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 β 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 β 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 β-barrel channels for various functional purposes.
Tian
Pu
P
Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 5 Memorial Drive, Room 201, Bethesda, MD 20892, USA. tianpu@jlu.edu.cn
Bernstein
Harris D
HD
D019453:Escherichia coli O157 / Q000201:enzymology*; D029968:Escherichia coli Proteins / Q000737:chemistry*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D055550:Protein Stability; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012697:Serine Endopeptidases / Q000737:chemistry*
D029968:Escherichia coli Proteins; C107189:EspP protein, E coli; D012697:Serine Endopeptidases