C-terminal kink formation is required for lateral gating in BamA.

Abstract:

:In Gram-negative bacteria, the outer membrane contains primarily β-barrel transmembrane proteins and lipoproteins. The insertion and assembly of β-barrel outer-membrane proteins (OMPs) is mediated by the β-barrel assembly machinery (BAM) complex, the core component of which is the 16-stranded transmembrane β-barrel BamA. Recent studies have indicated a possible role played by the seam between the first and last β-barrel strands of BamA in the OMP insertion process through lateral gating and a destabilized membrane region. In this study, we have determined the stability and dynamics of the lateral gate through over 12.5 μs of equilibrium simulations and 4 μs of free-energy calculations. From the equilibrium simulations, we have identified a persistent kink in the C-terminal strand and observed spontaneous lateral-gate separation in a mimic of the native bacterial outer membrane. Free-energy calculations of lateral gate opening revealed a significantly lower barrier to opening in the C-terminal kinked conformation; mutagenesis experiments confirm the relevance of C-terminal kinking to BamA structure and function.

authors

Lundquist K,Bakelar J,Noinaj N,Gumbart JC

doi

10.1073/pnas.1722530115

subject

Has Abstract

pub_date

2018-08-21 00:00:00

pages

E7942-E7949

issue

34

eissn

0027-8424

issn

1091-6490

pii

1722530115

journal_volume

115

pub_type

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