Role of stabilization centers in 4 helix bundle proteins

Stabilization centers (SCs) were shown to play an important role in preventing decay of three-dimensional protein structures. These residue clusters, stabilized by cooperative long-range interactions, were proposed to serve as anchoring points for arranging secondary structure elements. In all-a proteins, SC elements appear less frequently than in all-β, α/β, and α+β proteins suggesting that tertiary structure formation of all-α proteins is governed by different principles than in other protein classes. Here we analyzed the relation between the formation of stabilization centers and the interaxial angles (ω) of α-helices in 4 helix bundle proteins. In the distance range, where dipoles have dominant effect on the helix pair arrangement, those helix pairs, where residues from both helices participate in SC elements, appear as parallel more frequently than those helices where no SC elements are present. For SC containing helix pairs, the energetic difference between the parallel and anti-parallel states decreases considerably from 1.1 kcal/mol to 0.4 kcal/mol. Although the observed effect is weak for more distant helices, a competition between the SC element formation and the optimal dipole-dipole interaction of α-helices is proposed as a mechanism for tertiary structure formation in 4 helix bundle proteins. The SC-forming potential of different arrangements as well as the pitfalls of the SC definition are also discussed. © 2002 Wiley-Liss, Inc.