Protein Structure Representations

• Proteins have a sophisticated molecular structure, with fine tuning of the structure and activity developed over billions of years.
• The position of amino acids in a protein determines its 3D conformation which is stabilized by noncovalent interactions, with structure at the atomic level defining function.

Amino Acid Sequences

• Proteins consist of a chain of 20 different amino acids held together by covalent peptide bonds, forming polypeptides or polypeptide chains.
• Each protein has a unique amino acid sequence that dictate order.
• Millions of different proteins from different species are identified, having unique amino acid sequences.

Polypeptide Chains

• Each includes a backbone with chemical side chains.
• The polypeptide backbone consists of repeating core atoms (-N-C-C-).
• Each has two chemically different ends: an amino group (NH3+) and a carboxyl group (COO-).
• Each chain has directionality, with an amino terminus (N-terminus) and a carboxyl terminus (C-terminus).
• The amino acid side chains project, giving the protein their distinct properties like being nonpolar, polar uncharged, positively charged, or negatively charged.
• The sequence is read starting with the N-terminus, going left to right.
• Long chains are very flexible due to free rotation of carbon atoms in the polypeptide backbone.
• The shape of folded chains is constrained by weak noncovalent bonds.
• Atoms include polypeptide backbone and amino acid side chains.
• Noncovalent bonds include hydrogen bonds, electrostatic attractions, and van der Waals attractions.
• Many noncovalent bonds are required to tightly hold polypeptide regions together, which determines stability of the folded shape.
• Hydrophobic forces also determine protein shape.

Aqueous environments

• Nonpolar side chains of amino acids are forced together to minimize disruptive effect on hydrogen-bonded network of surrounding water molecules.
• Distribution of polar and nonpolar amino acids governs protein folding.
• Nonpolar side chains cluster inside of the folded protein to avoid contact with the aqueous environment.
• Polar side chains arrange near the outside of the folded protein to form hydrogen bonds with water and other polar molecules.
• Polar amino acids buried within the protein are hydrogen-bonded to other polar amino acids or to the polypeptide backbone.
• Numerous bonds and forces yield protein’s final folded structure.

Protein Folding

• Each type of protein has a particular 3D structure determined by the order of amino acids in its polypeptide chain.
• The final folded structure/conformation, is adopted by any polypeptide chain and is determined by energetic considerations.
• Proteins generally fold into a shape in free energy (G) is minimized.
• The folding process is energetically favorable.
• Protein folding has been studied in the lab using purified proteins.
• Proteins can be denatured using solvents that disrupt noncovalent bonds, folding the chain together.
• Protein spontaneously refolds into its original conformation when the denaturing solvent is removed, which is called renaturation.
• Denatured protein can refold into the correct conformation indicates that all the information to specify the 3D shape of a protein exists in its amino acid sequence.
• Protein folding in a living cell is generally assisted by chaperone proteins.
• Some chaperones bind to partly folded chains to help them fold along the most energetically favorable pathway.
• Other chaperones form "isolation chambers" where single polypeptide chains can fold without the risk of forming aggregates in the crowded cytoplasm.
• Chaperones make the process more efficient and reliable.

Protein Conformation

• Most proteins normally fold into a single, stable conformation.
• This will change slightly when it interacts with other molecules in the cell.
• Proteins are the most structurally diverse macromolecules in the cell.
• They range in size from 30 amino acids to more than 10,000, however, most are between 50 and 2000 amino acids long.
• Proteins can be globular or fibrous, and they can form filaments, sheets, rings, or spheres.
• The structures of more than 100,000 different proteins are determined.
• Most proteins have a three-dimensional conformation so intricate and irregular.
• HPr is a small bacterial transport protein that is only 88 amino acids long, which transports sugar into bacterial cells.
• The backbone model shows the overall organization of the polypeptide chain.
• The ribbon model shows the polypeptide backbone, emphasizing its most conspicuous folding patterns.
• The wire model includes the positions of the side chains useful for predicting which amino acids might be involved in the protein’s activity.
• The space-filling model provides a contour map of the protein surface which revels which amino acids are exposed on the surface to water, or other macromolecules.
• Structures of larger proteins or multiprotein complexes are even more complicated.

Protein Folding Patterns

• Scientists use computer-based tools to emphasize different protein features.
• Comparisons reveal that overall conformation is unique with regular folding patterns.
• Scientists studying hair and silk discovered a helices and β sheets.
• The a helix discovered was a-keratin protein which is abundant in skin and its derivatives.
• The ẞ sheet discovered were found in the protein fibroin, which is the major constituent of silk
• They result from hydrogen bonds that form between the N-H and C=O groups in the polypeptide backbone.
• Amino acid side chains are not involved in forming these hydrogen bonds, hence, a helices and β sheets are generated by many different amino acid sequences.
• The protein chain adopts a regular, repeating form.

Helices

• The abundance in proteins is generated by placing similar subunits next to one another, each in the same repeated relationship.
• Result in a structure which resembles a spiral staircase.
• Can be either right-handed or left-handed. which depends on the way it twists.
• The a helix is generated when a single polypeptide chain turns around itself to form a structurally rigid cylinder.
• Hydrogen bonds are made between every fourth amino acid, linking the C=O of one peptide bond to the N-H of another.
• Transmembrane proteins usually form an α helix, made of amino acids with nonpolar side chains.
• The polypeptide backbone which is hydrophilic is hydrogen-bonded to itself inside the a helix, shielded from lipid environment.
• Two or three a helices will wrap around one another to form a coiled-coil.

Beta Sheets

• Hydrogen bonds form between segments of a polypeptide chain that lie side by side.
• Neighboring segments run in the same orientation structure and form a parallel sheet.
• When segments run in opposite directions forming an antiparallel sheet.
• Both types produce produce a very rigid, pleated structure, forming the core of many proteins.
• Give silk fibers their extraordinary tensile strength.
• Form the basis of amyloid structures where sheets are stacked like the teeth of a zipper.

Misfolded Proteins and Amyloid Structures

• Cells specialized for secretion store peptide, structure allows for efficient packaging, and they unfold once they reach the cell exterior.
• Can also form amyloid structures which are harmful to cells.
• Damage cells and tissues.
• Contributes to neurodegenerative disorders, including Alzheimer's, Parkinson's, and Huntington's diseases.
• Prions are considered "infectious" because the amyloid form can convert properly folded molecules of the protein into the abnormal, disease-causing confirmation.
• The abnormal form causes the conversion of normal proteins in the host's brain into the misfolded prion form.
• Protein aggregation results causing neurodegenerative disorder.
• Amyloid disrupts brain-cell function.

Levels of Protein Organization

• Does not begin and end with a helices and ẞ sheets.
• Confirmation includes interdependent levels and builds one another.
• The amino acid sequence is the considered its primary structure.
• The a helices and ẞ sheets that form within certain segments of the polypeptide chain are the secondary structure, which is produced by backbone hydrogen bonding.
• The full, three-dimensional conformation formed by an entire is the tertiary structure.
• Noncovalent bonds form along the polypeptide chain, between amino acid side chains, and between side chains and the polypeptide backbone.
• If the protein molecule exists as more than one polypeptide chain, then interacting polypeptides form its quaternary structure and are held together by noncovalent bonds.
• The protein domain unit is defined as any segment of a that can fold independently into a compact, stable structure.
• A domain contains 40 and 350 amino acids.

Protein Domains

• Are the modular unit in proteins which can be constructed.
• Elements of secondary structure pack together into stable, independently folding, globular elements.
• A typical protein molecule consists of at least one domain which are linked by polypeptide chain.
• Different domains are often associated with different functions
• For example, the bacterial catabolite activator protein (CAP) has a domain which binds to DNA and another that binds cyclic AMP, a small intracellular signaling molecule.
• Binding cAMP causes a conformational change in the protein which enables small domains to bind a with DNA and promote expression of an adjacent gene.
• Small protein molecules a single.

Protein Regions

• Larger proteins have connected domains between polypeptide chain.
• Short, unstructured ubiquity sequences in proteins can bend and be flexible via thermal buffering.
• Sequences may have important function within a cell.

Polypeptide Chains

• Vast of chains theoretically made from amino acids.
• Potential chains have functional proteins which should be "well-behaved" and not engage in unwanted associations.

Protein Confirmation

• Diverse organisms have protein and consistuent confirmations and domains remain effective and the structure is preserved throughout evolution.

Protein Classifications

• proteins can be grouped into protein families if the amino acids resemble the structure from the original protein in which each family member has an amino acid sequence a three-dimensional conformation that closely resemble those of the other family members.
• Serine, Protein-cleaving, digestive enzymes which include chymotrypsin, trypsin, and elastase,.
• When two enzymes are compared, amino acid sequences nearly the same but activities have distinct enzymatic activity.

Large Protein Molecules

• Types of weak noncovalent bonds enable a poplypeptide.
• binding sites recognizes surface pf a second protein the binding will be a larger protein with a a precisely defined and organized, Each poplypeptide chain is a sunbit they contain one or more.doman
• dimer a complex of two the bacterail protein with one protein sun bit 80th contain two domain protein complexes multi ple copys of sunbit
• enyme neuraninadase consist og for indetucal protein subunit
• protein molecules contain two protein subunits and multiple subunits
• Protein sassemble in filaments sheets of splinters, the binding as the protien which is complementary to create other region on

Protein filaments

• Actan long heculical structure
• Protune assoiciate for tubes such is protein coat virus or spherical shell
• subunits can assemble and complex structure and have inly of the structure binding, which are dentinal sites.
• Fibrils and filament form protein shape most

Protein Shapes

• Most proteins, we have been referring to are globular proteins in which the poplypeptide folds into a compact shape, like a ball with and irregular surface while enzymes tended to be globular proteins, but even though They are large and complicated with multiple.
• units most have have a cordially structure with an
  Overall rounded shape but other proteins have roles in the cell and require them to expand large distance and generally have a relatively shapes.

Elongated Fibrous Proteins

• An akeratin molecule a dimer of two identical subunits with the long alicia's which form coiled
• These coiled coil region kept eat in by globular
  Domains contents binding sites to allow them to assemble and ropelike international fillament and the cell mechanical
• In multicellular the function of the extra are called
• Each has one glycine
• Matrix to help bind cells together to perform their job
• the function and structure, Each has been well

Explore different protein structure representations and their applications. Learn which representation is best for identifying overall shape, specific interactions, conserved motifs, and surface interactions. Understand why scientists use multiple representations and the role of computer-based tools.