Side-chain conformations in 4-α-helical bundles

Abstract

The distribution of the χ1, χ2 dihedral angles in a dataset consisting of 12 unrelated 4-α-helical bundle proteins was determined and qualitatively compared with that observed in globular proteins. The analysis suggests that the 4-α-helical bundle motif could occasionally impose steric constraints on side chains: (i) the side-chain conformations are limited to only a subset of the conformations observed in globular proteins and for some amino acids they are sterically more constrained than those in helical regions of globular proteins; (ii) aspartic acid and asparagine occasionally adopt rotamers that have not been previously reported for globular or helical proteins; (iii) some rotamers of tyrosine and isoleucine are predominantly or exclusively associated with hydrophobic core positions (a, d); (iv) mutations in the hydrophobic core occur preferentially between residue types which among other physicochemical properties also share a predominant rotamer.