Structure of Protein Part 2

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Slide 1 : • Secondary structure is the initial folding pattern (periodic repeats) of the linear polypeptide • 3 main types of secondary structure: a- helix, ß-sheet and bend/loop • Secondary structures are stabilized by hydrogen bonds Secondary Structure

Slide 2 :

Slide 3 : • The a-helix is right-handed or clock-wise • Each turn has 3.6 aa residues and is 5.4 Ao high • The helix is stabilized by H-bonds between –N-H and –C=O groups of every 4th amino acid • a-helices can wind around each other to form ‘coiled coils’ that are extremely stable and found in fibrous structural proteins such as keratin, myosin (muscle fibers) etc The a-helix

Slide 4 :

Slide 5 : • Extended stretches of 5 or more aa are called ß- strands • ß-strands organized next to each other make ß-sheets • If adjacent strands are oriented in the same direction (N-end to C-end), it is a parallel ß-sheet, if adjacent strands run opposite to each other, it is an antiparallel ß-sheet. There can also be mixed ß-sheets • H-bonding pattern varies depending on type of sheet • ß-sheets are usually twisted rather than flat • Fatty acid binding proteins are made almost entirely of ß-sheets ß-Pleated Sheet

Slide 6 :

Slide 7 : • Polypeptide chains can fold upon themselves forming a bend or a loop. • Usually 4 aa are required to form the turn • H-bond between the 1st and 4th aa in the turn • Bends are usually on the surface of globular proteins • Proline residues frequently found in bends / loops Bend / Loop

Slide 8 :

Slide 9 : • 3D folding or ‘bundling up’ of the protein • Non-polar residues are buried inside, polar residues are exposed outwards to aqueous environment • Many proteins are organized into multiple ‘domains’ • Domains are compact globular units that are connected by a flexible segment of the polypeptide • Each domain is contributes a specific function to the overall protein • Different proteins may share similar domain structures, eg: kinase-, cysteine-rich-, globin-domains Tertiary Structure

Slide 10 :

Slide 11 : • 5 kinds of bonds stabilize tertiary structure: H-bonds, van der waals interactions, hydrophobic interactions, ionic interactions and disulphide linkages • In disulphide linkages, the SH groups of two neighboring cysteines form a –S-S- bond called as a disulphide linkage. It is a covalent bond, but readily cleaved by reducing agents that supply the protons to form the SH groups again • Reducing agents include ß-mercaptoethanol Tertiary Structure

Slide 12 : • association of more than one polypeptides • Each unit of this protein is called as a subunit and the protein is an oligomeric protein • Subunits (monomers) can be identical or different • The protein is homopolymeric or heteropolymeric • Disulfide bonds usually stabilize the oligomer Quaternary Structure

Slide 13 :

Slide 14 : • Each protein has a unique and specific 3D structure that depends on the aa sequence. This is their native conformation. • Denaturing agents such as urea or guanidinium chloride disrupt the 3D structure. This is called denaturation • Denaturation is reversible. Removal of denaturants agents and sometimes, presence of a chaperones, is required for refolding • Protein folding is a cooperative ‘all or none’ process AA sequence dictates protein structure

Slide 15 : • Individual aa have a preference for specific 2o structure • a-helix (default): A, E, L, M, C • ß-sheets (steric clash): V, T, I, F, W, Y • Bends: P, G, N • No definite rules for 3o structure. Determined by overall sequence and tertiary interactions between remote residues; decrease in free energy. • Prediction based on computer calculations and comparison to similar domains of known structure Prediction of Protein Structure

Slide 16 : THANK YOU

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