@article{58df441d24544efa99061631e0288f01,
title = "Substrate binding to BamD triggers a conformational change in BamA to control membrane insertion",
abstract = "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.",
keywords = "Bam complex, Beta-barrel, Outer membrane, Protein folding",
author = "James Lee and Sutterlin, {Holly A.} and Wzorek, {Joseph S.} and Mandler, {Michael D.} and Hagan, {Christine L.} and Marcin Grabowicz and David Tomasek and May, {Mary D.} and Hart, {Elizabeth M.} and Silhavy, {Thomas J.} and Daniel Kahne",
note = "Funding Information: ACKNOWLEDGMENTS. We thank all members of the D.K. and T.J.S. laboratories for support and helpful comments and the Center for Macromolecular Interactions in the Department of Biological Chemistry and Molecular Pharmacology at Harvard Medical School for technical assistance with microscale thermophoresis. This work was supported by NIH Grants F31GM116210 (to J.L.), F32GM108258 (to J.S.W.), GM34821 and GM118024 (to T.J.S.), and AI081059 (to D.K.) and National Science Foundation Graduate Research Fellowship Program Awards DGE1148900 (to H.A.S.) and DGE1144152 (to M. D. Mandler). Funding Information: We thank all members of the D.K. and T.J.S. laboratories for support and helpful comments and the Center for Macromolecular Interactions in the Department of Biological Chemistry and Molecular Pharmacology at Harvard Medical School for technical assistance with microscale thermophoresis. This work was supported by NIH Grants F31GM116210 (to J.L.), F32GM108258 (to J.S.W.), GM34821 and GM118024 (to T.J.S.), and AI081059 (to D.K.) and National Science Foundation Graduate Research Fellowship Program Awards DGE1148900 (to H.A.S.) and DGE1144152 (to M. D. Mandler). Publisher Copyright: {\textcopyright} 2018 National Academy of Sciences. All Rights Reserved.",
year = "2018",
month = mar,
day = "6",
doi = "10.1073/pnas.1711727115",
language = "English (US)",
volume = "115",
pages = "2359--2364",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "10",
}