Question

1. a. Consider the following sequences, which are pieces of a larger, independently folding polypeptide. Which sequence is more likely to form an alpha helix, and which is more likely to form a beta-hairpin—a two-stranded antiparallel beta-sheet in which the strands are separated by a turn?

Sequence A: I F I C T T G P N A T V I C V F V

Sequence B: M D R L M E A M A K L D H L L A E

b. How do the structures of the residues I, V, and T versus L and M contribute to the conformational preferences of these two sequences?

c. Which residues likely form the turn between the stands in the beta-hairpin? Why are these residues suited for this structure?

Answer 1

a) Sequence A is more likely to form beta-hairpin secondary structure due to certain residues such as I, V, T, G, P.

Sequence B is more likely to form alpha helix secondary structure.

b) Residues such as I (Isoleucine), V (Valine), and T (Threonine) causes steric hindrance due to branches at beta carbon and thus does not support the formation of alpha helix. Such amino acids usually form beta pleated sheets. Other amino acids like L (Leucine) and M (Methionine) has no such branches on the beta carbon and thus do not cause steric clashes in alpha helix formation.

c) Proline (P) and Glycine (G) residues are usually found in the turns between the strands. Glycine being the simplest amino acid with simplest side chain is sterically flexible, and proline due to its cyclic structure is mostly seen in loops and turns. Proline has no -NH group and thus cannot form hydrogen bond with the carbonly group in alpha helix or beta pleated sheets.