Molecular Basis for the Structural Stability of an Enclosed β-Barrel Loop

We present molecular dynamics simulation studies of the structural stability of an enclosed loop in the beta domain of the Escherichia coli O157: H7 autotransporter EspP. Our investigation revealed that, in addition to its excellent resistance to thermal perturbations, EspP loop 5 (L5) also has remarkable mechanical stability against pulling forces along the membrane norm. These findings are consistent with the experimental report that EspP L5 helps to maintain the permeability barrier in the outer membrane. In contrast to the major secondary structure elements of globular proteins such as ubiquitin, whose resistance to thermal and mechanical perturbations depends mainly on backbone hydrogen bonds and hydrophobic interactions, the structural stability of EspP L5 can be attributed mainly to geometric constraints and side-chain interactions dominated by hydrogen bonds. Examination of B-factors from available high-resolution structures of membrane-embedded beta barrels indicates that most of the enclosed loops have stable structures. This finding suggests that loops stabilized by geometric constraints and side-chain interactions might be used more generally to restrict beta-barrel channels for various functional purposes. (C) 2010 Elsevier Ltd. All rights reserved.