Protein Presentation: Keratin Group: Mike Dibley Chris Geiger Noel Barkhooy

Keratin Fibrous (structural) proteins. Individual molecules combine to form insoluble structures. Keratins are the molecular basis for hair, nails, wool, feathers, beaks, claws and horns. Keratin is also found in the cytoskeleton of cells. Keratin clusters are found on chromosomes 12 and 17.

alpha (cysteine rich) isomer found in cytoskeleton and hair. beta (cysteine poor) isomer found mostly in birds and reptiles. It is the building block of scales, feathers and claws. It is rich in residues with small side chains: glycine, alanine and serine. alpha form can be stretched up to 120% in moist heat. beta form is rigid. Cysteine can form disulfide bridges with other cysteine residues. These cross-linkages decrease the elasticity of alpha-keratin.

In the early 1950s Linus Pauling and R.B. Corey in proposed several structures for keratin. Observed shorter than expected amide C-N bond. They deduced that the peptide bond was planar. A planar peptide bond reduced the number of conformations of a poly-peptide chain and led to their proposal of the alpha helix and the beta sheet. alpha-helix explained the x-ray data which showed a repeat unit of 0.50 – 0.55 nm. This distance corresponds to the height of the rise per revolution of helix. alpha-helix also explained a repeat unit of 0.15 nm. This distance corresponds to the height of the rise per residue. The ratio of these two numbers give the number of amino acids per revolution: 3.6 Hydrogen bonding occurs between carbonyl oxygen and the amide hydrogen on next twist of helix.

There are many forms of alpha-keratin. Individual alpha-keratin molecules all follow the same pattern: head, rod and tail (100:300:100). The rod section contains 3 individual alpha-helices with short interleaving sections separating them. Type I (40-55 kDa) are acidic. (k9-k20) Type II (56-70 kDa) are neutral or basic. (k1-k8) Many of the subclasses contain allelic versions (there are 6 forms of k6 (human)). Two type I and two type II molecules form a heterotetramer. The arrangement of this molecule is a left-handed coil.

Cytokeratin 3, type II Cytokeratin 12, type I

Helical Structure Continued In a coil group of 7 residues, 1st & 4th positions contain hydrophobic aa’s These nonpolar aa’s on different helical chains attract each other and make up the inside positions of the double coils These hydrophobic reactions stabilize the coil structure The outside positions are mostly polar aa’s

Homology Type I & II keratins actually share a low homology; <30% at nuc. Acid level High homology between same type keratins ~60-90% Suggests a major sequence divergence So although the aa sequences may differ significantly the structures the proteins take on is always the same “coiled coil” and interact with each other

The End