Protein Structure Foundation Block Dr Usman Ghani What

Protein Structure (Foundation Block) Dr. Usman Ghani • What are proteins? • Four levels of structure (primary, secondary, tertiary, quaternary) • Protein folding and stability • Protein denaturation • Protein misfolding and diseases

What are proteins? n Proteins are polymers of amino acids joined together by peptide bonds

Primary Structure n It is the linear sequence of amino acids

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Secondary Structure It is the local three-dimensional arrangement of a polypeptide backbone n Excluding the conformations (3 D arrangements) of its side chains n

a Helix n n n a helix is right-handed It has 3. 6 residues (amino acids) per turn The helix is stabilized by hydrogen bonding u Between carboxylic group and 4 th N–H group The amino acid side chains point outward and downward from the helix The core of the helix is tightly packed; its atoms are in van der Waals contact

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b Sheets Two or more polypeptide chains form hydrogen bonding with each other n Also called pleated sheets n They appear as folded structures with edges n

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Antiparallel b sheets Two or more hydrogen-bonded polypeptide chains run in opposite direction n Hydrogen bonding is more stable n

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Parallel b sheets Two or more hydrogen-bonded polypeptide chains run in the same direction n Hydrogen bonding is less stable (distorted) n

Other secondary structures Turns (reverse turns) n Loops n b bends n Random coils n

n Supersecondary structures or motifs: ubab motif: a helix connects two b sheets ub hairpin: reverse turns connect antiparallel b sheets uaa motif: two a helices together ub barrels: rolls of b sheets

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Tertiary Structure It is the three-dimensional structure of an entire polypeptide chain including side chains n It is the folding of secondary structure and side chains n Helices, sheets and side chains combined to form tertiary structure n

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n Domains u. Polypeptide chains (>200 amino acids) fold into two or more clusters known as domains u. Domains are units that look like globular proteins u. Domains are part of protein subunits

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Quaternary Structure Many proteins contain two or more polypeptide chains n Each chain forms a three-dimensional structure called subunit n It is the 3 D arrangement of different subunits of a protein n

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n Hemoglobin is a globular protein u. A multisubunit protein is called oligomer u. Composed of a 2 b 2 subunits (4 chains, 4 subunits) u. Two same subunits are called protomers

Protein folding Forces that stabilize proteins n Protein denaturation n

Forces that stabilize protein structure Hydrophobic effect: u. Nonpolar groups to minimize their contacts with water u. Nonpolar side chains are in the interior of a protein n Hydrogen bonding n

Electrostatic interactions (ion pairing): u. Between positive and negative charges n van der Waals forces (weak polar forces): u. Weak attractive or repulsive forces between molecules n

Protein denaturation n n Denaturation: A process in which a protein looses its native structure Factors that cause denaturation: u Heat: disrupts hydrogen bonding u Change in p. H: alters ionization states of aa u Detergents: interfere with hydrophobic interactions u Chaotropic agents: ions or small organic molecules that disrupt hydrophobic interactions

Protein misfolding Every protein must fold to achieve its normal conformation and function n Abnormal folding of proteins leads to a number of diseases in humans Alzheimer’s disease: n b-amyloid protein is a misfolded protein n It forms fibrous deposits or plaques in the brains of Alzheimer’s patients n

Creutzfeldt-Jacob or prion disease: n Piron protein is present in normal brain tissue n In diseased brains, the same protein is misfolded n Therefore it forms insoluble fibrous aggregates that damage brain cells

That’s all folks!