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Characterization of the ABC methionine transporter from Neisseria meningitidis reveals that lipidated MetQ is required for interaction

Sharaf, Naima G. and Shahgholi, Mona and Kim, Esther and Lai, Jeffrey Y. and VanderVelde, David G. and Lee, Allen T. and Rees, Douglas C. (2021) Characterization of the ABC methionine transporter from Neisseria meningitidis reveals that lipidated MetQ is required for interaction. eLife, 10 . Art. No. e69742. ISSN 2050-084X. PMCID PMC8416018. doi:10.7554/eLife.69742.

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NmMetQ is a substrate-binding protein (SBP) from Neisseria meningitidis that has been identified as a surface-exposed candidate antigen for meningococcal vaccines. However, this location for NmMetQ challenges the prevailing view that SBPs in Gram-negative bacteria are localized to the periplasmic space to promote interaction with their cognate ABC transporter embedded in the bacterial inner membrane. To elucidate the roles of NmMetQ, we characterized NmMetQ with and without its cognate ABC transporter (NmMetNI). Here, we show that NmMetQ is a lipoprotein (lipo-NmMetQ) that binds multiple methionine analogs and stimulates the ATPase activity of NmMetNI. Using single-particle electron cryo-microscopy, we determined the structures of NmMetNI in the presence and absence of lipo-NmMetQ. Based on our data, we propose that NmMetQ tethers to membranes via a lipid anchor and has dual function and localization, playing a role in NmMetNI-mediated transport at the inner membrane and moonlighting on the bacterial surface.

Item Type:Article
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URLURL TypeDescription CentralArtlce Paper
Sharaf, Naima G.0000-0002-3662-9228
Lai, Jeffrey Y.0000-0003-2863-4411
VanderVelde, David G.0000-0002-2907-0366
Rees, Douglas C.0000-0003-4073-1185
Alternate Title:Characterization of the ABC methionine transporter from Neisseria meningitidis reveals that MetQ is a lipoprotein
Additional Information:© 2021, Sharaf et al. This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited. Received: 24 April 2021; Preprinted: 04 May 2021; Accepted: 18 August 2021; Published: 19 August 2021. We thank Jacob Parres-Gold and Dr. Sara J Weaver for useful discussions and Dr. Lilien Voong for critical reading of the manuscript. We also thank Dr. Songye Chen and Dr. Andrey Malyutin of the Beckman Institute Resource Center for Transmission Electron Microscopy at Caltech for assistance with data collection. This research utilized instrumentation made available by the Caltech CCE Multiuser Mass Spectrometry Laboratory, the CCE Liquids NMR Facility, and the Beckman Institute cryo-EM facility. NGS was supported by the Postdoctoral Enrichment Program from the Burroughs Wellcome Fund and DCR is a Howard Hughes Medical Institute Investigator. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Author Contributions: Naima G Sharaf, Conceptualization, Data curation, Formal analysis, Supervision, Funding acquisition, Validation, Investigation, Visualization, Methodology, Writing - original draft, Project administration, Writing - review and editing; Mona Shahgholi, Resources, Formal analysis, Investigation, Methodology, Writing - original draft, Writing - review and editing; Esther Kim, Validation, Investigation, Methodology; Jeffrey Y Lai, Software, Methodology; David G VanderVelde, Resources, Methodology; Allen T Lee, Resources, Investigation, Writing - review and editing; Douglas C Rees, Conceptualization, Data curation, Supervision, Funding acquisition, Project administration, Writing - review and editing. The authors declare that no competing interests exist. Data availability: For NmMetNI in the inward-facing conformation and lipo-NmMetQ:NmMetNI complex in the outward-facing conformation, cryoEM maps have been deposited in the Electron Microscopy Data Bank (EMDB) under accession codes EMD-23752 and EMD-23751. Coordinates for the model are deposited in the Research Collaboratory for Structural Bioinformatics Protein Data Bank under accession numbers 7MC0 and 7MBZ, respectively.
Funding AgencyGrant Number
Burroughs Wellcome FundUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
PubMed Central ID:PMC8416018
Record Number:CaltechAUTHORS:20210506-075107170
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Official Citation:Characterization of the ABC methionine transporter from Neisseria meningitidis reveals that lipidated MetQ is required for interaction. eLife 2021; 10:e69742; DOI: 10.7554/eLife.69742
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:108980
Deposited By: Tony Diaz
Deposited On:06 May 2021 18:56
Last Modified:16 Sep 2021 17:37

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