Conformational changes in the essential E. coli septal cell wall synthesis complex suggest an activation mechanism

Bibliographic Details
Main Author: Britton, Brooke M.
Publication Date: 2023
Other Authors: Yovanno, Remy A., Costa, Sara F., McCausland, Joshua, Lau, Albert Y., Xiao, Jie, Hensel, Zach
Format: Article
Language: eng
Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Download full: http://hdl.handle.net/10362/165712
Summary: Funding Information: The authors thank all members of the Hensel, Xiao, and Lau laboratories for helpful discussions and feedback on the manuscript. Z.H. received support for this work from FCT—Fundação para a Ciência e a Tecnologia, I.P., through MOSTMICRO-ITQB R&D Unit (UIDB/04612/2020, UIDP/04612/2020, Z.H.) and LS4FUTURE Associated Laboratory (LA/P/0087/2020, Z.H.), from a joint research agreement with the Okinawa Institute of Science and Technology, and from the Google Cloud Research Credits program with the award GCP20210916. S.F.C. received support from FCT Fundação para a Ciência e a Tecnologia, I.P., through a PhD fellowship (PD/BD/135480/2018, SMC). Work in the Xiao laboratory was supported by NIH F32GM143895 (B.M.B.), NIH T32GM007445 (J.W.M), and R35GM136436 (J.X.). Work in the Lau laboratory was funded by the Johns Hopkins Catalyst Award (to A.Y.L.); NIH T32GM135131 (to R.A.Y.). Anton 2 computer time (MCB130045P) was provided by the Pittsburgh Supercomputing Center (PSC) through NIH grant R01GM116961 (to A.Y.L.); the Anton 2 machine at PSC was generously made available by D.E. Shaw Research. We also used resources provided by Advanced Research Computing at Hopkins (ARCH) at Johns Hopkins University. Funding Information: The authors thank all members of the Hensel, Xiao, and Lau laboratories for helpful discussions and feedback on the manuscript. Z.H. received support for this work from FCT—Fundação para a Ciência e a Tecnologia, I.P., through MOSTMICRO-ITQB R&D Unit (UIDB/04612/2020, UIDP/04612/2020, Z.H.) and LS4FUTURE Associated Laboratory (LA/P/0087/2020, Z.H.), from a joint research agreement with the Okinawa Institute of Science and Technology, and from the Google Cloud Research Credits program with the award GCP20210916. S.F.C. received support from FCT Fundação para a Ciência e a Tecnologia, I.P., through a PhD fellowship (PD/BD/135480/2018, SMC). Work in the Xiao laboratory was supported by NIH F32GM143895 (B.M.B.), NIH T32GM007445 (J.W.M), and R35GM136436 (J.X.). Work in the Lau laboratory was funded by the Johns Hopkins Catalyst Award (to A.Y.L.); NIH T32GM135131 (to R.A.Y.). Anton 2 computer time (MCB130045P) was provided by the Pittsburgh Supercomputing Center (PSC) through NIH grant R01GM116961 (to A.Y.L.); the Anton 2 machine at PSC was generously made available by D.E. Shaw Research. We also used resources provided by Advanced Research Computing at Hopkins (ARCH) at Johns Hopkins University. Publisher Copyright: © 2023, The Author(s).
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spelling Conformational changes in the essential E. coli septal cell wall synthesis complex suggest an activation mechanismChemistry(all)Biochemistry, Genetics and Molecular Biology(all)Physics and Astronomy(all)Funding Information: The authors thank all members of the Hensel, Xiao, and Lau laboratories for helpful discussions and feedback on the manuscript. Z.H. received support for this work from FCT—Fundação para a Ciência e a Tecnologia, I.P., through MOSTMICRO-ITQB R&D Unit (UIDB/04612/2020, UIDP/04612/2020, Z.H.) and LS4FUTURE Associated Laboratory (LA/P/0087/2020, Z.H.), from a joint research agreement with the Okinawa Institute of Science and Technology, and from the Google Cloud Research Credits program with the award GCP20210916. S.F.C. received support from FCT Fundação para a Ciência e a Tecnologia, I.P., through a PhD fellowship (PD/BD/135480/2018, SMC). Work in the Xiao laboratory was supported by NIH F32GM143895 (B.M.B.), NIH T32GM007445 (J.W.M), and R35GM136436 (J.X.). Work in the Lau laboratory was funded by the Johns Hopkins Catalyst Award (to A.Y.L.); NIH T32GM135131 (to R.A.Y.). Anton 2 computer time (MCB130045P) was provided by the Pittsburgh Supercomputing Center (PSC) through NIH grant R01GM116961 (to A.Y.L.); the Anton 2 machine at PSC was generously made available by D.E. Shaw Research. We also used resources provided by Advanced Research Computing at Hopkins (ARCH) at Johns Hopkins University. Funding Information: The authors thank all members of the Hensel, Xiao, and Lau laboratories for helpful discussions and feedback on the manuscript. Z.H. received support for this work from FCT—Fundação para a Ciência e a Tecnologia, I.P., through MOSTMICRO-ITQB R&D Unit (UIDB/04612/2020, UIDP/04612/2020, Z.H.) and LS4FUTURE Associated Laboratory (LA/P/0087/2020, Z.H.), from a joint research agreement with the Okinawa Institute of Science and Technology, and from the Google Cloud Research Credits program with the award GCP20210916. S.F.C. received support from FCT Fundação para a Ciência e a Tecnologia, I.P., through a PhD fellowship (PD/BD/135480/2018, SMC). Work in the Xiao laboratory was supported by NIH F32GM143895 (B.M.B.), NIH T32GM007445 (J.W.M), and R35GM136436 (J.X.). Work in the Lau laboratory was funded by the Johns Hopkins Catalyst Award (to A.Y.L.); NIH T32GM135131 (to R.A.Y.). Anton 2 computer time (MCB130045P) was provided by the Pittsburgh Supercomputing Center (PSC) through NIH grant R01GM116961 (to A.Y.L.); the Anton 2 machine at PSC was generously made available by D.E. Shaw Research. We also used resources provided by Advanced Research Computing at Hopkins (ARCH) at Johns Hopkins University. Publisher Copyright: © 2023, The Author(s).The bacterial divisome is a macromolecular machine composed of more than 30 proteins that controls cell wall constriction during division. Here, we present a model of the structure and dynamics of the core complex of the E. coli divisome, supported by a combination of structure prediction, molecular dynamics simulation, single-molecule imaging, and mutagenesis. We focus on the septal cell wall synthase complex formed by FtsW and FtsI, and its regulators FtsQ, FtsL, FtsB, and FtsN. The results indicate extensive interactions in four regions in the periplasmic domains of the complex. FtsQ, FtsL, and FtsB support FtsI in an extended conformation, with the FtsI transpeptidase domain lifted away from the membrane through interactions among the C-terminal domains. FtsN binds between FtsI and FtsL in a region rich in residues with superfission (activating) and dominant negative (inhibitory) mutations. Mutagenesis experiments and simulations suggest that the essential domain of FtsN links FtsI and FtsL together, potentially modulating interactions between the anchor-loop of FtsI and the putative catalytic cavity of FtsW, thus suggesting a mechanism of how FtsN activates the cell wall synthesis activities of FtsW and FtsI.Instituto de Tecnologia Química e Biológica António Xavier (ITQB)RUNBritton, Brooke M.Yovanno, Remy A.Costa, Sara F.McCausland, JoshuaLau, Albert Y.Xiao, JieHensel, Zach2024-04-02T23:18:10Z2023-122023-12-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/165712eng2041-1723PURE: 71562215https://doi.org/10.1038/s41467-023-39921-4info:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2024-05-22T18:20:06Zoai:run.unl.pt:10362/165712Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-28T17:50:51.308278Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv Conformational changes in the essential E. coli septal cell wall synthesis complex suggest an activation mechanism
title Conformational changes in the essential E. coli septal cell wall synthesis complex suggest an activation mechanism
spellingShingle Conformational changes in the essential E. coli septal cell wall synthesis complex suggest an activation mechanism
Britton, Brooke M.
Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)
title_short Conformational changes in the essential E. coli septal cell wall synthesis complex suggest an activation mechanism
title_full Conformational changes in the essential E. coli septal cell wall synthesis complex suggest an activation mechanism
title_fullStr Conformational changes in the essential E. coli septal cell wall synthesis complex suggest an activation mechanism
title_full_unstemmed Conformational changes in the essential E. coli septal cell wall synthesis complex suggest an activation mechanism
title_sort Conformational changes in the essential E. coli septal cell wall synthesis complex suggest an activation mechanism
author Britton, Brooke M.
author_facet Britton, Brooke M.
Yovanno, Remy A.
Costa, Sara F.
McCausland, Joshua
Lau, Albert Y.
Xiao, Jie
Hensel, Zach
author_role author
author2 Yovanno, Remy A.
Costa, Sara F.
McCausland, Joshua
Lau, Albert Y.
Xiao, Jie
Hensel, Zach
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Tecnologia Química e Biológica António Xavier (ITQB)
RUN
dc.contributor.author.fl_str_mv Britton, Brooke M.
Yovanno, Remy A.
Costa, Sara F.
McCausland, Joshua
Lau, Albert Y.
Xiao, Jie
Hensel, Zach
dc.subject.por.fl_str_mv Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)
topic Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)
description Funding Information: The authors thank all members of the Hensel, Xiao, and Lau laboratories for helpful discussions and feedback on the manuscript. Z.H. received support for this work from FCT—Fundação para a Ciência e a Tecnologia, I.P., through MOSTMICRO-ITQB R&D Unit (UIDB/04612/2020, UIDP/04612/2020, Z.H.) and LS4FUTURE Associated Laboratory (LA/P/0087/2020, Z.H.), from a joint research agreement with the Okinawa Institute of Science and Technology, and from the Google Cloud Research Credits program with the award GCP20210916. S.F.C. received support from FCT Fundação para a Ciência e a Tecnologia, I.P., through a PhD fellowship (PD/BD/135480/2018, SMC). Work in the Xiao laboratory was supported by NIH F32GM143895 (B.M.B.), NIH T32GM007445 (J.W.M), and R35GM136436 (J.X.). Work in the Lau laboratory was funded by the Johns Hopkins Catalyst Award (to A.Y.L.); NIH T32GM135131 (to R.A.Y.). Anton 2 computer time (MCB130045P) was provided by the Pittsburgh Supercomputing Center (PSC) through NIH grant R01GM116961 (to A.Y.L.); the Anton 2 machine at PSC was generously made available by D.E. Shaw Research. We also used resources provided by Advanced Research Computing at Hopkins (ARCH) at Johns Hopkins University. Funding Information: The authors thank all members of the Hensel, Xiao, and Lau laboratories for helpful discussions and feedback on the manuscript. Z.H. received support for this work from FCT—Fundação para a Ciência e a Tecnologia, I.P., through MOSTMICRO-ITQB R&D Unit (UIDB/04612/2020, UIDP/04612/2020, Z.H.) and LS4FUTURE Associated Laboratory (LA/P/0087/2020, Z.H.), from a joint research agreement with the Okinawa Institute of Science and Technology, and from the Google Cloud Research Credits program with the award GCP20210916. S.F.C. received support from FCT Fundação para a Ciência e a Tecnologia, I.P., through a PhD fellowship (PD/BD/135480/2018, SMC). Work in the Xiao laboratory was supported by NIH F32GM143895 (B.M.B.), NIH T32GM007445 (J.W.M), and R35GM136436 (J.X.). Work in the Lau laboratory was funded by the Johns Hopkins Catalyst Award (to A.Y.L.); NIH T32GM135131 (to R.A.Y.). Anton 2 computer time (MCB130045P) was provided by the Pittsburgh Supercomputing Center (PSC) through NIH grant R01GM116961 (to A.Y.L.); the Anton 2 machine at PSC was generously made available by D.E. Shaw Research. We also used resources provided by Advanced Research Computing at Hopkins (ARCH) at Johns Hopkins University. Publisher Copyright: © 2023, The Author(s).
publishDate 2023
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2023-12-01T00:00:00Z
2024-04-02T23:18:10Z
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