OF MICE AND MEN: DISSECTING THE INTERACTION BETWEEN LISTERIA MONOCYTOGENES INTERNALIN A AND E-CADHERIN

Computational and Structural Biotechnology Journal

卷:6

Samuel Genheden¹  Leif A Eriksson¹ 

[1] Division of Physical Chemistry, Department of Chemistry and Molecular Biology, University of Gothenburg, SE-41296, Gothenburg, Sweden;

关键词: Internalin A;    E-cadherin;    molecular dynamics;    energy decomposition;    umbrella sampling;   

DOI  :  10.5936/csbj.201303022

来源: DOAJ

【 摘 要 】

We report a study of the interaction between internalin A (inlA) and human or murine E-cadherin (Ecad). inlA is used by Listeria monocytogenes to internalize itself into host cell, but the bacterium is unable to invade murine cells, which has been attributed to the difference in sequence between hEcad and mEcad. Using molecular dynamics simulations, MM/GBSA free energy calculations, hydrogen bond analysis, water characterization and umbrella sampling, we provide a complete atomistic picture of the binding between inlA and Ecad. We dissect key residues in the protein–protein interface and analyze the energetics using MM/GBSA.'From this analysis it is clear that the binding of inlA–mEcad is weaker than inlA–hEcad, on par with the experimentally observed inability of inlA to bind to mEcad.'However, extended MD simulations of 200 ns in length show no destabilization of the inlA–mEcad complex and the estimation of the potential of mean force (PMF) using umbrella sampling corroborates this conclusion. The binding strength computed from the PMFs show no significant difference between the two protein complexes. Hence, our study suggests that the inability of L. monocytogenes to invade murine cells cannot be explained by processes at the nanosecond to sub-microsecond time scale probed by the simulations performed here.

【 授权许可】

Unknown