Analysis and design of turns in α-helical hairpins

Abstract

Although the analysis and design of turns that connect the strands in antiparallel β-hairpins has reached an advanced state, much less is known concerning turns between antiparallel helices in helical hairpins. We have conducted an analysis of the structures and sequence preferences of two types of interhelical turns, each of which connects the two helices by a two-residue linker in an αL-β conformation. Based on this analysis, it became apparent that the turn introduced into a designed four-helix bundle protein, DF1, did not occur within an optimal structural context. DF1 is a dimeric model for the diiron class of proteins. A longer loop with a β-αR-β conformation was inserted between two helices in the protein, and a sequence was chosen to stabilize its conformation. X-ray crystallography and NMR analysis of the protein showed the structure to be in excellent agreement with design. © 2004 Elsevier Ltd. All rights reserved.