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Multiple conformational states and gate opening of outer membrane protein TolC revealed by molecular dynamics simulations
Author(s) -
Wang Beibei,
Weng Jingwei,
Wang Wenning
Publication year - 2014
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.24573
Subject(s) - periplasmic space , bacterial outer membrane , biophysics , molecular dynamics , chemistry , membrane , protein structure , mutant , crystallography , biochemistry , biology , computational chemistry , escherichia coli , gene
Outer membrane protein TolC serves as an exit duct for exporting substances out of cell. The occluded periplasmic entrance of TolC is required to open for substrate transport, although the opening mechanism remains elusive. In this study, systematic molecular dynamics (MD) simulations for wild type TolC and six mutants were performed to explore the conformational dynamics of TolC. The periplasmic gate was shown to sample multiple conformational states with various degrees of gating opening. The gate opening was facilitated by all mutations except Y362F, which adopts an even more closed state than wild type TolC. The interprotomer salt‐bridge R367–D153 is turned out to be crucial for periplasmic gate opening. The mutations that disrupt the interactions at the periplasmic tip may affect the stability of the trimeric assembly of TolC. Structural asymmetry of the periplasmic gate was observed to be opening size dependent. Asymmetric conformations are found in moderately opening states, while the most and the least opening states are often more symmetric. Finally, it is shown that lowering pH can remarkably stabilize the closed state of the periplasmic gate. Proteins 2014; 82:2169–2179. © 2014 Wiley Periodicals, Inc.