Protein.pdf

PROTEIN One of the most diverse biomolecules on earth is proteins. Following are the biological functions performed by Proteins 1. Catalyzing various cellular reactions: Enzymes 2. Structural components: Microtubules, Actin Filament and Intermedi...

PROTEIN One of the most diverse biomolecules on earth is proteins. Following are the biological functions performed by Proteins 1. Catalyzing various cellular reactions: Enzymes 2. Structural components: Microtubules, Actin Filament and Intermediate Filaments,collagen 3. Transportation of various molecules: Plasma proteins, Hb 4. Motor molecules: carry membrane-enclosed organelles, Actin and myosin 5. Transmission of cell-to-cell communication 6. Protection by identifying and flagging invaders etc. -Antibiotics, snake venom https://www.youtube.com/watch?v=iB7B0YaSLhU For all these functions to occur respective protein needs to be in a specific conformation. This unique conformation of a protein is a result of specific differences between each amino acids and their intra-molecular interactions as well as interactions with the environment. Combined, the similarities and differences between amino acids explain how cells can build a diverse pool of proteins from the same set of building blocks. Irrespective of the structure or function all proteins are composed of twenty standard L-α-amino acids often called as building blocks of proteins. Amino Acids: Amino acids are building blocks of protein. Following is the general structure of amino acid. All building blocks consist of a central carbon atom, a carboxyl group, a side chain attached to a central carbon atom and a primary amino group but one i.e. proline consists of a secondary amino group which is a part of a five member ring. The fourth α-carbon bond may link to another single hydrogen atom, as in glycine, or to a group of atoms as mentioned above as a side chain. This side chain range in size, polarity or charge hence each amino acid is unique in nature. The variations mentioned above lead to various interactions by each of these amino acids, which individually as well as collectively contribute to the stability and functioning of the protein as a biomolecule. From the pool of these building blocks polymer protein is synthesized at the cellular level. Transcription of the genes encoded in the DNA is read by m-RNA which begins the protein synthesis. The code information is via translation given to t-RNA which picks the respective amino acid from the pool of amino acids. The pool also contains amino acids other than standard one like 4-hydroxyproline, 5-hydroxylysine, N-formylmethionine, γ- carboxyglutamic acid, which are modified amino acids. The pool also contains α-Aminobutyric acid (which is also known as homoalanine), β-Aminobutyric acid and γ-Butyric acid. Homoalanine can be a monomer for non-ribosomal peptide synthase while, β-Aminobutyric acid and γ-Butyric acid act as neurotransmitter. https://www.youtube.com/watch?v=eGy_5p2VcOs Classification of amino acids Glucogenic or Glucogenic and Glycogenic Ketogenic  Conceptual hierarchy including four levels of protein structure are defined and described as follows: 1. Primary structure: This level deals with the basic backbone of protein describing covalent peptide bonds giving information of amino acid sequence which is genetically coded. The native conformation and hence the unique properties of the protein including  the catalytic activity and conformational stability is determined by the sequence of the amino acids in a polypeptide2. 2. Secondary structure: This level refers to the local spatial arrangements of short segments of amino acid sequence in the shape of helices, pleated sheets and turns which are the regular polypeptide backbone folding patterns. Driving forces for these structures are mainly non-covalent interactions such as hydrogen bonds and electrostatic interactions between side chains. It refers to the spatial arrangements of amino acids residues that are adjacent in a segment of a polypeptide3. 3. Tertiary structure: This level describes the three dimensional folding of secondary structures to the way of native conformation. Apart from hydrogen bonding and electrostatic interactions, hydrophobic interactions play an important role in the three dimensional arrangement of a molecule. It includes longer-range aspects of the amino acids sequence i.e. amino acids that are far apart in the polypeptide sequence and are in different types of secondary structure of a protein4. 4. Quaternary structure: This level characterizes interaction of two or more folding protein3. https://www.youtube.com/watch?v=EweuU2fEgjw Protein Synthesis:https://www.youtube.com/watch?v=G8RYhV569xg Considering the higher levels of structure, proteins can be classified into two classes: fibrous proteins in which arrangement of polypeptide chains is seen in a long strands or sheets, and the other class includes globular proteins, with polypeptide chains folded into a spherical or globular shape3. Sequence of amino acids determines protein folding, which influences the overall shape of the protein. Protein shape, in turn, influences the function of protein. Anything that is capable of altering the shape of a protein has a potential to reduce or eliminate that protein’s function and can potentially impact survival of the cell.  The stability in considering protein structure can be defined as the tendency to maintain a native conformation of a protein which is a net balance of forces. Protein misfolding can occur either during translation or as a consequence of some change in the environment of the cell, while certain stress conditions like improper pH, high concentration of salt or urea, high temperature can lead to protein unfolding. Various interactions involved in protein stabilisation can be as follows: Hydrophobic interactions: The force of association in case of protein stability is mainly hydrophobic interactions which are weak but preferred over repulsion of hydrophobic groups with water medium. The burial of hydrophobic groups is more or less 85%. It is observed that the contribution of hydrophobic effect varies with size of protein more or less proportionately but always with greater than 50% contribution to protein stability. Still theoretical studies are needed in gaining more knowledge in terms of the relative contribution of van der Waals effect and classic hydrophobic effect to the overall contribution of hydrophobic interaction to protein structure stabilization. Hydrogen bond interactions: After hydrophobic interactions hydrogen bonds make a larger contribution to protein stability. Investigation shows that it is an important factor and contributes to stability of protein to greater extent. Along with non polar groups, burial of polar groups which are uncharged also takes place which increases complexity in understanding interactions as it involves hydrogen bonding as well as long range coulombic interactions. Van der Waals interactions: Another non covalent interaction which plays an important role in protein stability is Van der Waals interactions. Electrostatic interactions: electrostatic interactions leading to salt bridge formation can also influence stability and functionality of protein molecules. Certain salt bridges do stabilise helices. A small effect on stability of protein on introduction of charged sites suggests that these types of interactions are weak. Disulphide linkage in protein structure: Apart from peptide covalent bond protein structure entails one more type of covalent bond i.e. disulphide linkage. In fact, formation of disulphide bonds is one of the crucial steps which leads to folding in many proteins which are secretary. This linkage is between two cys residues on the protein backbone chain. This also plays an important role in protein conformation. Recent study on anticancer activity where recombinant protein is made, incorporates disulfide bond as one of the important factor for stability of recombinant protein. The extracellular region of neural cells entails adhesion molecules containing immunoglobulin-like domains having dimers interlinked with disulphide bonds.