Structural and sequence characteristics of long α helices in globular proteins

Abstract

Elucidation of the detailed structural features and sequence requirements for α helices of various lengths could be very important in understanding secondary structure formation in proteins and, hence, in the protein folding mechanism. An algorithm to characterize the geometry of an α helix from its C^α coordinates has been developed and used to analyze the structures of long α helices (number of residues ≥ 25) found in globular proteins, the crystal structure coordinates of which are available from the Brookhaven Protein Data Bank. All long α helices can be unambiguously characterized as belonging to one of three classes: linear, curved, or kinked, with a majority being curved. Analysis of the sequences of these helices reveals that the long α helices have unique sequence characteristics that distinguish them from the short alpha helices in globular proteins. The distribution and statistical propensities of individual amino acids to occur in long α helices are different from those found in short α helices, with amino acids having longer side chains and/or having a greater number of functional groups occurring more frequently in these helices. The sequences of the long α helices can be correlated with their gross structural features, i.e., whether they are curved, linear, or kinked, and in case of the curved helices, with their curvature.