Substrate binding to BamD triggers a conformational change in BamA to control membrane insertion.

TitleSubstrate binding to BamD triggers a conformational change in BamA to control membrane insertion.
Publication TypeJournal Article
Year of Publication2018
AuthorsLee, J, Sutterlin, HA, Wzorek, JS, Mandler, MD, Hagan, CL, Grabowicz, M, Tomasek, D, May, MD, Hart, EM, Silhavy, TJ, Kahne, D
JournalProc Natl Acad Sci U S A
Volume115
Issue10
Pagination2359-2364
Date Published2018 03 06
ISSN1091-6490
KeywordsBacterial Outer Membrane Proteins, Escherichia coli Proteins, Kinetics, Models, Molecular, Periplasm, Protein Binding, Protein Conformation, Protein Folding
Abstract

<p>The β-barrel assembly machine (Bam) complex folds and inserts integral membrane proteins into the outer membrane of Gram-negative bacteria. The two essential components of the complex, BamA and BamD, both interact with substrates, but how the two coordinate with each other during assembly is not clear. To elucidate aspects of this process we slowed the assembly of an essential β-barrel substrate of the Bam complex, LptD, by changing a conserved residue near the C terminus. This defective substrate is recruited to the Bam complex via BamD but is unable to integrate into the membrane efficiently. Changes in the extracellular loops of BamA partially restore assembly kinetics, implying that BamA fails to engage this defective substrate. We conclude that substrate binding to BamD activates BamA by regulating extracellular loop interactions for folding and membrane integration.</p>

DOI10.1073/pnas.1711727115
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID29463713
PubMed Central IDPMC5877925
Grant ListR35 GM118024 / GM / NIGMS NIH HHS / United States
R01 GM034821 / GM / NIGMS NIH HHS / United States
T32 GM007388 / GM / NIGMS NIH HHS / United States
F32 GM108258 / GM / NIGMS NIH HHS / United States
R01 AI081059 / AI / NIAID NIH HHS / United States
R37 GM034821 / GM / NIGMS NIH HHS / United States
F31 GM116210 / GM / NIGMS NIH HHS / United States