Bio2B03 Module 1 Lecture 1 Script PDF

BIO 2B03 Module scripts Module 1, lecture 1 +-----------------------+-----------------------+-----------------------+ | | Script | Notes | +=======================+=======================+=======================+ | Slide 1 | Hi ever...

BIO 2B03 Module scripts Module 1, lecture 1 +-----------------------+-----------------------+-----------------------+ | | Script | Notes | +=======================+=======================+=======================+ | Slide 1 | Hi everyone, and | | | | welcome to BIOLOGY | | | | 2B03- Cell Biology. | | | | As a blended learning | | | | course, **BIO2B03** | | | | Is course that will | | | | cover a broad array | | | | of interconnected | | | | themes. This will | | | | include considering | | | | how proteins are | | | | made, their | | | | structure, their | | | | function , and for | | | | those who do so... | | | | how some proteins | | | | exit the cell. | | | | | | | | We will also explore | | | | a number of ways that | | | | a cell is able to | | | | perceive signals from | | | | each other and their | | | | environment, and how | | | | the response to these | | | | signals often results | | | | in short term or long | | | | term cellular | | | | changes. | | | | | | | | Finally, we will | | | | explore how cell | | | | division is a very | | | | controlled and | | | | regulated process | | | | which eventually | | | | results in mitosis | | | | and the division of | | | | one cell into two | | | | identical daughter | | | | cells.  This is a | | | | process that's | | | | especially important | | | | for many tissues in | | | | our body.  | | | | | | | | But, all cells also | | | | have a shelf-life.  | | | | During times of | | | | stress, damage or | | | | when triggered by | | | | pre-programmed | | | | cellular signals, a | | | | cell will undergo | | | | self-destruction | | | | through a process | | | | called apoptosis | | | | | | | | But before we get | | | | started with these | | | | interesting topics, | | | | we have to start with | | | | basic principles. | | | | | | | | Today, we will get | | | | started with our | | | | first Lecture for | | | | Module 1, From | | | | polypeptide to | | | | protein, where we | | | | will explore our | | | | different amino acids | | | | and their chemical | | | | interactions. Let's | | | | get started! | | +-----------------------+-----------------------+-----------------------+ | Slide 2 | The objectives for | | | | this module are to | | | | review the principles | | | | of the primary | | | | structure of a | | | | polypeptide, to take | | | | an overview of the of | | | | the properties of | | | | amino acid variable | | | | side chains (or | | | | R‐groups), and to | | | | describe the chemical | | | | interactions | | | | essential to protein | | | | structure. | | +-----------------------+-----------------------+-----------------------+ | Slide 3 | What is a protein? | | | | What are the | | | | functions of | | | | proteins? I want you | | | | to take a moment just | | | | to pause and think | | | | about your definition | | | | of a protein and | | | | think about what | | | | proteins do in the | | | | cell. | | | | | | | | You might've come up | | | | with the definition | | | | of proteins such as a | | | | string of amino | | | | acids, a polypeptide | | | | chain or a polymer of | | | | other small | | | | molecules. | | | | | | | | When you think about | | | | the function of | | | | proteins, we can | | | | basically answer that | | | | by saying proteins do | | | | everything. | | | | | | | | Some examples you | | | | might have come up | | | | with could include | | | | the fact that | | | | | | | | - Proteins are | | | | structural | | | | components of the | | | | cell, (tubules, | | | | actins and | | | | cytoskeletal | | | | elements) | | | | | | | | - that proteins are | | | | sensors for | | | | environmental | | | | change and that | | | | they may help | | | | with mechanisms | | | | for relaying | | | | information from | | | | the outside of | | | | the cell to the | | | | inside of the | | | | cell, initiating | | | | changes in cell | | | | behavior. | | | | | | | | - You may also | | | | remember that | | | | proteins are | | | | enzymes that can | | | | metabolize | | | | chemical | | | | reactions. | | | | | | | | - Or that proteins | | | | can regulate gene | | | | expression | | | | (acting as | | | | activators or | | | | silencers that | | | | allow or inhibit | | | | gene expression) | | | | | | | | - Proteins could | | | | also be modifiers | | | | that change the | | | | function of other | | | | proteins, turning | | | | proteins on and | | | | off. We also know | | | | that proteins are | | | | signals that are | | | | produced by | | | | cells, and are | | | | required for | | | | signaling between | | | | cells. And of | | | | course, proteins | | | | are also | | | | receptors that | | | | receive those | | | | signals, and they | | | | are the | | | | components of the | | | | transduction | | | | pathways that | | | | interpret those | | | | signals. | | | | | | | | - Or maybe you were | | | | thinking, | | | | proteins form | | | | molecular motors, | | | | in that they are | | | | able to transport | | | | components around | | | | the cell. | | | | | | | | - Or that proteins | | | | are important for | | | | the unique | | | | identity and | | | | function of | | | | membrane‐bound | | | | organelles in the | | | | cell. | | | | | | | | All of these | | | | functions are true, | | | | and all functions | | | | outline the | | | | importance of | | | | proteins in all of | | | | our cells! | | +-----------------------+-----------------------+-----------------------+ | Slide 4 | How can one type of | | | | molecule accomplish | | | | all of this? Unlike | | | | RNA and DNA, which | | | | assume a limited | | | | number of structures, | | | | there is a virtually | | | | an unlimited number | | | | of molecular | | | | structures that | | | | proteins can assume. | | | | | | | | Each protein has its | | | | own unique, defined | | | | structure that | | | | enables it to carry | | | | out a particular | | | | function. | | | | | | | | If we look at the | | | | structure of proteins | | | | we could see that | | | | there is a diverse | | | | array of what | | | | proteins can look | | | | like: diversity in | | | | size and diversity in | | | | structure. The | | | | | | | | shape and structure | | | | of a protein is | | | | ultimately going to | | | | | | | | specify function of | | | | the protein. | | | | | | | | We see here, some | | | | examples of enzymes | | | | such as glutamine | | | | synthetase that forms | | | | a large donut‐shape | | | | structure with an | | | | active domain in the | | | | middle. | | | | | | | | We see smaller | | | | globular proteins | | | | such as the signal | | | | insulin or the | | | | oxygen‐ carrying | | | | protein complex | | | | hemoglobin. | | | | | | | | We also see here, the | | | | typical Y shape of | | | | the immunoglobulin | | | | protein that is | | | | necessary for | | | | recognizing antigens, | | | | viruses and bacteria, | | | | in the cell and | | | | removing them. | | | | | | | | Finally, we see a | | | | smaller enzyme over | | | | at the right hand | | | | side, adenylate | | | | kinase, containing a | | | | structure that is | | | | essential for | | | | defining the | | | | substrate binding | | | | domain and the | | | | activity domain for | | | | this enzyme. | | +-----------------------+-----------------------+-----------------------+ | Slide 5 | Proteins are composed | | | | of amino acids. | | | | | | | | The linear array of | | | | amino acids is the | | | | primary structure. We | | | | see here, 5 amino | | | | acids that have been | | | | strung together to | | | | form a small | | | | polypeptide. One | | | | amino acid residue in | | | | the chain is circled | | | | in green. Each core | | | | central alpha carbon | | | | is shown with the | | | | associated variable | | | | side chain. In this | | | | primary sequence, | | | | these variable side | | | | chains are R~1~ R~2~ | | | | R~3~, etc from left | | | | to right or from | | | | N‐terminus to | | | | C‐terminus- that is, | | | | amino end to carboxyl | | | | end. | | | | | | | | Connecting each of | | | | these amino acids | | | | together to form a | | | | chain of amino acid | | | | residues are peptide | | | | bonds. The peptide | | | | bonds are represented | | | | here by the orange | | | | line between a | | | | carboxyl group and | | | | amino group. | | | | | | | | We have a total of 20 | | | | possible different | | | | amino acids that can | | | | be incorporated into | | | | newly synthesized | | | | polypeptides or | | | | proteins. We will see | | | | later that even after | | | | a polypeptide is | | | | formed, post‐ | | | | translational | | | | modifications can | | | | alter the properties | | | | of | | | | | | | | individual amino | | | | acids, and as a | | | | result, the | | | | properties of a | | | | protein, as a whole. | | +-----------------------+-----------------------+-----------------------+ +-----------------------+-----------------------+-----------------------+ | Slide 6 | A single amino acid | | | | is represented here. | | | | The 20 possible amino | | | | acids all have the | | | | same basic structure. | | | | The central alpha | | | | carbon has four side | | | | chains: | | | | | | | | - a hydrogen side | | | | chain | | | | | | | | - an amino group | | | | | | | | - a carboxyl group | | | | | | | | - and the variable | | | | R group. | | | | | | | | It is the variable R | | | | group that is going | | | | to define the | | | | property of each | | | | amino acid residue, | | | | but it is the | | | | accumulated R groups | | | | that are going to | | | | define the properties | | | | of a polypeptide or | | | | protein. | | +=======================+=======================+=======================+ | Slide 7 | Since the the | | | | R-groups or side | | | | chains of amino acids | | | | are essential to | | | | understanding the | | | | properties of | | | | proteins, we need to | | | | think about how these | | | | side chains differ | | | | from one another. We | | | | will look at the | | | | properties of the | | | | individual side | | | | chains. But keep in | | | | mind that what is | | | | important are the | | | | emergent properties | | | | that come from the | | | | **interactions** of | | | | all the side chains | | | | in a protein. | | | | | | | | These interactions | | | | will determine how | | | | the protein folds and | | | | it will determine the | | | | characteristics of | | | | the whole protein. | | | | | | | | The amino acid side | | | | chains differ in | | | | their size, shape, | | | | charge, | | | | hydrophobicity, and | | | | reactivity. Cell | | | | biologists classify | | | | these amino acid | | | | residue side chains | | | | into groups based | | | | upon their solubility | | | | in water or the | | | | polarity of the side | | | | chain. | | +-----------------------+-----------------------+-----------------------+ | Slide 8 | Solubility is a | | | | physical property of | | | | a molecule that | | | | refers to its ability | | | | to transiently | | | | interact with water | | | | through hydrogen | | | | bonding. This is | | | | thermodynamically | | | | favorable. | | | | | | | | So- if hydrogen bonds | | | | can form with water, | | | | the molecule can be | | | | soluble. If a | | | | molecule cannot form | | | | these hydrogen bonds, | | | | then it is insoluble. | | | | | | | | A soluble protein | | | | typically carries | | | | hydrophilic amino | | | | acid residues on the | | | | external surface. In | | | | contrast hydrophobic | | | | molecules are not | | | | polarized and cannot | | | | form these hydrogen | | | | bonds, so...water | | | | repels these | | | | molecules in favor of | | | | bonding with itself. | | +-----------------------+-----------------------+-----------------------+ | | What sorts of | | | | molecules are | | | | hydrophobic? Really, | | | | anything that is | | | | unable to form a | | | | hydrogen bond. | | | | | | | | Typically we think of | | | | oil or fats that do | | | | not mix with water. | | | | Now, why do they not | | | | interact with water? | | | | Well, because these | | | | oils or fat contain | | | | saturated hydrophobic | | | | long carbon chains | | | | called hydrocarbons. | | | | | | | | We can then extend | | | | this to our amino | | | | acid residues. We can | | | | look for those amino | | | | acid residue side | | | | chains that have | | | | these types of | | | | hydrocarbon chains. | | | | | | | | Hydrophobic amino | | | | acids have types of | | | | non‐polar side chains | | | | and are water | | | | insoluble, or perhaps | | | | only slightly | | | | soluble. Because of | | | | this, these amino | | | | acids tend to be | | | | found in the interior | | | | of cytosolic proteins | | | | and form a | | | | hydrophobic core. | | | | | | | | But keep in mind, | | | | that a protein found | | | | in a hydrophobic | | | | environment (such as | | | | a protein that's | | | | embedded in a | | | | membrane), for these | | | | proteins, they will | | | | have the opposite | | | | structure with the | | | | hydrophobic amino | | | | acids accumulating on | | | | the exterior of the | | | | protein, facing | | | | towards the | | | | phospholipid tails of | | | | the membrane layer. | | +-----------------------+-----------------------+-----------------------+ | | We can divide the | | | | hydrophobic amino | | | | acid residues into 2 | | | | categories: aromatic | | | | amino acids and | | | | aliphatic amino | | | | acids. | | | | | | | | Phenylalanine, | | | | tyrosine and | | | | tryptophan have | | | | hydrophobic aromatic | | | | rings in their | | | | R-groups. These | | | | aromatic rings are | | | | very hydrophobic. | | | | Note that as cell | | | | biologists, we have | | | | placed tyrosine into | | | | this hydrophobic | | | | category, yet it does | | | | have a hydroxyl group | | | | on the end of its | | | | R-group, a group that | | | | is capable of forming | | | | a hydrogen bond. So | | | | really tyrosine falls | | | | into both categories, | | | | both hydrophobic and | | | | hydrophilic. | | | | | | | | At the right, we have | | | | our 5 hydrophobic, | | | | aliphatic amino | | | | acids. Notice that | | | | the R-groups for | | | | these amino acids | | | | have long hydrocarbon | | | | chains. | | | | | | | | Alanine has just one | | | | methyl side chain, | | | | valine isoleucine, | | | | leucine, and | | | | methionine all have | | | | longer hydrocarbon | | | | chains. Notice also | | | | that methionine has a | | | | | | | | sulfur within its | | | | chain. | | | | | | | | Overall, amino acids | | | | with aromatic or | | | | aliphatic R-groups | | | | (or side chains) will | | | | be classified as | | | | hydrophobic. | | +-----------------------+-----------------------+-----------------------+ | | What about | | | | hydrophilic amino | | | | acid residues? | | | | | | | | Hydrophilic molecules | | | | are water soluble, | | | | and for that reason | | | | we find our | | | | hydrophilic amino | | | | acid residues on the | | | | exterior of soluble | | | | cytosolic proteins. | | | | Water soluble | | | | molecules have | | | | portions that are | | | | charge- polarized and | | | | capable of forming | | | | hydrogen bonds. | | | | | | | | Remember this is | | | | relevant to our cells | | | | at a physiological | | | | pH- a pH of 7. So | | | | we're looking at | | | | molecules with a | | | | hydroxyl group or a | | | | charged oxygen at pH | | | | 7, or molecules that | | | | have this amino group | | | | with a positive | | | | charge at a pH of 7. | | +-----------------------+-----------------------+-----------------------+ | | Here we see examples | | | | of amino acids that | | | | carry | | | | | | | | charged side chains. | | | | | | | | On the left, amino | | | | acids with positively | | | | charged side chains, | | | | lysine and arginine. | | | | | | | | On the right, amino | | | | acids with negatively | | | | charged side chains, | | | | aspartic acid and | | | | glutamic acid. | | | | | | | | These four amino | | | | acids are | | | | hydrophilic, and are | | | | prime contributors to | | | | the overall charge of | | | | a protein or a domain | | | | of a protein. | | +-----------------------+-----------------------+-----------------------+ | | There are also | | | | uncharged, polar | | | | hydrophilic amino | | | | acid residues. | | | | | | | | Shown here are the | | | | amino acids threonine | | | | and serine, with | | | | polar hydroxyl groups | | | | that can participate | | | | in hydrogen bonds, | | | | and asparagine and | | | | glutamine that are | | | | uncharged but have | | | | these polar amine | | | | groups. | | +-----------------------+-----------------------+-----------------------+ | | Finally, we have a | | | | collection of special | | | | amino acid residues. | | | | | | | | - Cysteine is a | | | | special amino | | | | acid, because it | | | | is able to form | | | | covalent bonds, | | | | through its | | | | sulfur atom, with | | | | other cysteine | | | | amino acids. | | | | These covalent | | | | bonds are called | | | | disulfide bridges | | | | or cysteine | | | | bridges | | | | | | | | - Glycine is | | | | special because | | | | it is very small. | | | | The side chain is | | | | a single | | | | hydrogen. The | | | | small size of | | | | glycine allows | | | | for it to tuck in | | | | small places in a | | | | folding protein | | | | and allow for | | | | bends in a | | | | polypeptide | | | | chain. | | | | | | | | - Proline is | | | | special because | | | | it's R- group | | | | forms a covalent | | | | bond with the | | | | amino group of | | | | the amino acid. | | | | This can lead to | | | | a kink or bend | | | | forming in a | | | | polypeptide | | | | chain, that is | | | | essential for the | | | | structure of many | | | | proteins | | | | | | | | - And finally, we | | | | have our amino | | | | acid histidine, | | | | which has an | | | | amino diethyl | | | | side chain, that | | | | shifts between a | | | | positive charge | | | | and neutral | | | | charge, depending | | | | on the pH of the | | | | environment | | | | | | | | For our course, make | | | | sure you review all | | | | of the properties of | | | | the amino acid side | | | | chains. We will not | | | | ask you to draw the | | | | structures of these | | | | amino acids, but you | | | | should be able to | | | | recognize and know | | | | the unique properties | | | | of all 20 amino | | | | acids. Knowing these | | | | properties will be | | | | essential for us to | | | | understand the unique | | | | structure and | | | | function of different | | | | proteins. | | +-----------------------+-----------------------+-----------------------+ | | To make a protein, | | | | amino acids must be | | | | covalently bound | | | | together through | | | | peptide bonds. A | | | | peptide bond is | | | | formed by a | | | | condensation | | | | reaction, which | | | | simply means that | | | | water is released | | | | during the formation | | | | of this covalent | | | | bond. | | | | | | | | Here we have two | | | | amino acids side by | | | | side. We can see the | | | | carboxyl group of the | | | | amino acid on the | | | | left and the amino | | | | group of the amino | | | | acid on the right. | | | | Through a | | | | condensation | | | | reaction, one | | | | molecule of water is | | | | released and a | | | | peptide bond is | | | | formed. | | +-----------------------+-----------------------+-----------------------+ | | Protein chains are | | | | typically depicted | | | | from left to right, | | | | from N‐terminus (or | | | | amino end) to | | | | C‐terminus (or | | | | carboxyl end). | | | | Protein synthesis | | | | takes place during | | | | the process of | | | | translation. During | | | | this process of | | | | translation, new | | | | amino acid residues | | | | are added to the | | | | carboxyl end. As a | | | | result, the | | | | N‐terminus of any | | | | protein is the first | | | | amino acid in the | | | | chain and subsequent | | | | amino acids are added | | | | to the carboxyl end, | | | | that is, the right | | | | hand end of the | | | | growing chain. | | +-----------------------+-----------------------+-----------------------+ | | Translation happens | | | | in the ribosome. | | | | Shown here is a video | | | | animation of the | | | | process of | | | | translation from | | | | | | | | the Howard Hughes | | | | Medical Institute's | | | | collection of | | | | BioInteractives. | | +-----------------------+-----------------------+-----------------------+ | | Video, no script | | +-----------------------+-----------------------+-----------------------+ +-----------------------+-----------------------+-----------------------+ | | Let's think a little | | | | bit about how we get | | | | from a polypeptide to | | | | something that is | | | | actually functional | | | | in the cell. Seen | | | | here, on the left | | | | hand side we have a | | | | representation of a | | | | polypeptide string, a | | | | linear array of amino | | | | acids that is not | | | | functional yet in the | | | | cell. We need a | | | | three‐dimensional | | | | protein such as the | | | | one on the right that | | | | has a series of loops | | | | and bends and sheets | | | | that define | | | | structural and | | | | functional domains | | | | within the protein. | | | | The structure on the | | | | right is dependent | | | | upon the amino acid | | | | sequence that we see | | | | on the left. But\-- | | | | it is not simply that | | | | amino acid sequence | | | | that is going to | | | | allow us to get to | | | | our three- | | | | dimensional | | | | structure. We are | | | | going to see that the | | | | polypeptide has to be | | | | modified in various | | | | ways in | | | | | | | | order to allow for | | | | this folding to | | | | occur. | | +=======================+=======================+=======================+ | | There are four levels | | | | of organization to | | | | get from a sequence | | | | of amino acids to a | | | | functional 3‐ | | | | dimensional protein. | | | | The primary structure | | | | is that | | | | | | | | linear array of amino | | | | acids. | | +-----------------------+-----------------------+-----------------------+ | | The primary structure | | | | of the polypeptide is | | | | the linear array or | | | | sequence of amino | | | | acids and is | | | | determined by the | | | | sequence of | | | | nucleotides in the | | | | coding DNA. | | | | | | | | This image represents | | | | the processes of | | | | transcription and | | | | translation that lead | | | | to the synthesis of a | | | | polypeptide chain. | | | | | | | | - To start, a | | | | sequence from the | | | | double‐ stranded | | | | DNA helix is | | | | transcribed into | | | | a single‐ | | | | stranded | | | | messenger RNA. | | | | | | | | - That messenger | | | | RNA is processed | | | | to remove introns | | | | and produce a | | | | mature messenger | | | | RNA, which | | | | essentially | | | | contains only the | | | | codons that are | | | | required for the | | | | synthesis of the | | | | protein. | | | | | | | | - The mature | | | | messenger RNA | | | | molecule is then | | | | exported out of | | | | the nucleus into | | | | the cytosol of | | | | the cell, where | | | | it is translated | | | | by the ribosome. | | | | | | | | So, the amino acid | | | | sequence is | | | | determined by that | | | | nucleotide sequence | | | | in the original | | | | associated gene. | | | | | | | | The number of | | | | different polypeptide | | | | sequences is limited | | | | by two factors: | | | | | | | | 1\) there are 20 | | | | distinct amino | | | | acids that can | | | | become incorporated | | | | into a polypeptide, | | | | | | | | 2\) the number of | | | | amino acid found in | | | | that polypeptide. | | | | | | | | So for any | | | | polypeptide string | | | | that is "n" amino | | | | acids long, the | | | | number of different | | | | arrangements of amino | | | | acids in a chain | | | | would be defined by | | | | 20 to the power of | | | | "n". Given this, we | | | | can see that there | | | | are infinite number | | | | of polypeptide | | | | sequences that could | | | | be produced in a | | | | cell. | | +-----------------------+-----------------------+-----------------------+ +-----------------------+-----------------------+-----------------------+ | | Polypeptides fold | | | | spontaneously and | | | | assume what is called | | | | a random‐coil | | | | structure. A | | | | random‐coil is best | | | | described as a | | | | periodically ordered | | | | structure of the | | | | protein. Proteins | | | | might not have a | | | | single stable | | | | structure, but a | | | | collection of related | | | | structures that they | | | | switch between. The | | | | term **statistical | | | | coil** is a | | | | representation of | | | | this idea and | | | | suggests that the | | | | protein spends most | | | | of its time in a | | | | particular structure, | | | | but not 100% of its | | | | time. This structure | | | | may be stabilized by | | | | interactions within | | | | the polypeptide, but | | | | also interactions | | | | with other proteins | | | | and other molecules | | | | as well. | | | | | | | | The structure that | | | | the polypeptide | | | | assumes most of the | | | | time, or **native | | | | structure**, is the | | | | functional protein | | | | structure. | | | | | | | | The local | | | | interactions that | | | | maintain protein | | | | shape are for the | | | | most part | | | | non‐covalent | | | | interactions that | | | | include ionic bonds | | | | and hydrogen bonds, | | | | Van der Waals forces | | | | and what is called | | | | the hydrophobic | | | | effect. Individually, | | | | these are weak | | | | attractive forces, | | | | | | | | but in their | | | | aggregate they form a | | | | very strong | | | | association, and | | | | provide stability to | | | | the folded protein | | | | structure. | | +=======================+=======================+=======================+ | | Let's step through | | | | each of these | | | | interactions. | | | | | | | | First of all, the | | | | ionic bond. This is | | | | an attraction between | | | | a positively charged | | | | cation and a | | | | negatively charged | | | | anion. Represented | | | | here in this image, | | | | is the interaction | | | | between glutamate and | | | | lysine, where we have | | | | a positively charged | | | | cation on the lysine | | | | side chain and a | | | | negatively charged | | | | anion on the | | | | glutamate side chain. | | | | If we look at this in | | | | the context of a | | | | simple polypeptide, | | | | we can see that this | | | | ionic interaction is | | | | assisting in holding | | | | the two arms of the | | | | polypeptide together | | | | in this shape. | | | | | | | | Now one bond isn't | | | | going to be enough to | | | | do that, but we're | | | | going to see how an | | | | accumulation of these | | | | interactions can | | | | maintain | | | | | | | | protein shape. | | +-----------------------+-----------------------+-----------------------+ | | A hydrogen bond is | | | | the interaction | | | | between a partially | | | | charged hydrogen atom | | | | in a molecular | | | | dipole, such as what | | | | we see in water, and | | | | an unpaired electron | | | | from another atom. | | | | | | | | Represented at the | | | | bottom right hand | | | | corner here is a | | | | polarized covalent | | | | bond, where there is | | | | not a full charge, | | | | but a partial charge | | | | or dipole moment. In | | | | a water molecule, | | | | oxygen has a partial | | | | negative charge, a | | | | negative dipole, | | | | whereas the hydrogen | | | | is exhibiting a | | | | partial positive | | | | charge, or a positive | | | | dipole. This can | | | | happen not only in | | | | water molecules, but | | | | in other covalent | | | | bonds as well. | | | | Represented here as | | | | well, is a hydrogen | | | | bond that is forming | | | | between the molecular | | | | dipoles at different | | | | side chains of two | | | | distinct amino acid | | | | residues. The | | | | hydrogen bond | | | | contributes here to | | | | protein shape | | +-----------------------+-----------------------+-----------------------+ | | Hydrophobic effects | | | | are the aggregation | | | | of nonpolar molecules | | | | in aqueous medium, | | | | simply to reduce the | | | | number of | | | | interactions with | | | | water. An example of | | | | this would be an oil | | | | droplet in water. All | | | | of the hydrophobic | | | | molecules aggregate | | | | together to minimize | | | | the surface area that | | | | is exposed to the | | | | hydrophilic aqueous | | | | environment. The | | | | aqueous environment | | | | of the cytosol can | | | | similarly induce | | | | these hydrophobic | | | | effects for | | | | hydrophobic amino | | | | acids in proteins. | | +-----------------------+-----------------------+-----------------------+ | | A Van der Waal's | | | | interaction, which is | | | | also known as London | | | | Dispersion forces, is | | | | a weak non‐specific | | | | attractive force. It | | | | results from a | | | | transient dipole that | | | | is induced when two | | | | atoms are very close | | | | together and they | | | | perturb the | | | | distribution of | | | | electrons in each | | | | other. This transient | | | | dipole only exists | | | | when these atoms are | | | | close to one another. | | | | The association that | | | | occurs though is not | | | | a strong one, it is | | | | not as strong as a | | | | hydrogen bond or | | | | ionic bond, but if we | | | | accumulate many of | | | | these Van der Waal's | | | | forces together, | | | | these interactions | | | | can be quite strong | | | | together. | | +-----------------------+-----------------------+-----------------------+ | | Let's take a look at | | | | an organismal example | | | | of Van der Waal's | | | | interactions -- the | | | | amazing ability of a | | | | gecko to walk on | | | | walls and ceilings. | | | | How is this possible? | | | | At the bottom of this | | | | slide, we see a | | | | close‐up of | | | | | | | | the gecko's foot. If | | | | we take an even | | | | closer look at the | | | | surface of its feet | | | | (as we see on the | | | | right), we can see | | | | structures called | | | | setae. These setae | | | | are small little | | | | fibers that are | | | | present on the | | | | surface of these | | | | feet. Each one of | | | | these little setae | | | | induces a transient | | | | dipole with the | | | | underlying surface | | | | causing a Van der | | | | Waal's interaction. | | | | Now one seta would | | | | not be enough to hold | | | | a gecko in place, | | +-----------------------+-----------------------+-----------------------+ | |... but when there | | | | are millions of these | | | | together, all on the | | | | entire surface of the | | | | foot, we find a very | | | | strong interaction. | | | | It is the sum | | | | strength of all of | | | | these Van der Waals | | | | interactions that | | | | allow geckos to walk | | | | along the ceiling. | | | | This is a neat | | | | observation, because | | | | we can use this to | | | | model adhesive | | | | surfaces. We can do | | | | this by looking at | | | | nanotubes that are | | | | mimicking the setae | | | | that we find in gecko | | | | feet. | | | | | | | | Similarly, in | | | | proteins, individual | | | | Van der Waal's | | | | interactions are very | | | | weak attractive | | | | forces. But the | | | | accumulated effect of | | | | many bonds like | | | | these, makes for a | | | | very strong overall | | | | association between | | | | two different | | | | proteins or within a | | | | protein. | | +-----------------------+-----------------------+-----------------------+ | | Folding is the result | | | | of interactions | | | | between amino acid | | | | residues t hat hold a | | | | polypeptide into | | | | shape. | | | | | | | | Here is a short | | | | animation that shows | | | | a polypeptide | | | | folding. Before we | | | | get started, keep in | | | | mind a few things: | | | | | | | | 1\) The color of the | | | | spheres and the | | | | type of | | | | interactions that | | | | can occur. Here, | | | | red spheres are | | | | representing amino | | | | acids with | | | | hydrophobic chains, | | | | purple and blue | | | | spheres are | | | | representing amino | | | | acids that can form | | | | hydrogen bonds, and | | | | yellow and green | | | | represent amino | | | | acids that can form | | | | ionic bonds. These | | | | interactions are | | | | important in | | | | allowing the | | | | peptide to form a | | | | three‐dimensional | | | | structure. | | | | | | | | 2\) Remember that | | | | folding is a random | | | | process; bonds are | | | | forming and bonds | | | | are also breaking | | | | as different bonds | | | | form. Folding is | | | | dynamic. | | | | | | | | 3\) Folding depends | | | | upon the number and | | | | the strength of | | | | bonds and | | | | interactions that | | | | are maintaining | | | | protein | | | | conformation. | | | | | | | | 4\) Also, note that | | | | for simplicity, in | | | | this animation, the | | | | arms of the | | | | polypeptide move | | | | through one | | | | another, that would | | | | be like us walking | | | | | | | | through a wall. It | | | | doesn't happen in an | | | | actual protein, but | | | | it is just shown to | | | | help us visualize the | | | | animation. | | +-----------------------+-----------------------+-----------------------+ | | I n this animation, | | | | we start with a short | | | | polypeptide. The grey | | | | spheres are amino | | | | acids, their specific | | | | identities do not | | | | affect folding. The | | | | polypeptide begins to | | | | fold and takes on a | | | | shape. Again, keep in | | | | mind that this is a | | | | random process. The | | | | polypeptide might | | | | unfold, but then it | | | | might fold again. The | | | | hydrophobic side | | | | chains in this | | | | polypeptide are going | | | | to aggregate together | | | | in a hydrophobic | | | | core, that | | | | hydrophobic core is | | | | also important in | | | | stabilizing the | | | | protein. Remember | | | | that hiding those | | | | hydrophobic side | | | | chains is | | | | thermodynamically | | | | favorable. We see | | | | bonds beginning to | | | | form, blue and purple | | | | form a hydrogen bond | | | | that is holding those | | | | arms together in | | | | | | | | that particular | | | | conformation. Yellow | | |