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A conserved membrane protein negatively regulates Mce1 complexes in mycobacteria
Open accessPreprint — published as 10.1038/s41467-023-41578-y · Paper page
Abstract
Tuberculosis continues to pose a serious threat to global health. Mycobacterium tuberculosis , the causative agent of tuberculosis, is an intracellular pathogen that relies on various mechanisms to survive and persist within the host. Among their many virulence factors, mycobacteria encode Mce systems. Some of these systems are implicated in lipid uptake, but the molecular basis for Mce function(s) is poorly understood. To gain insights into the composition and architecture of Mce systems, we characterized the putative Mce1 complex involved in fatty acid transport. We show that the Mce1 system in Mycobacterium smegmatis comprises a canonical ATP-binding cassette transporter, associated with functionally redundant heterohexameric assemblies of substrate-binding proteins. Furthermore, we establish that the conserved membrane protein Mce1N negatively regulates Mce1 function via a unique mechanism involving blocking transporter assembly. Our work offers molecular understanding of Mce complexes, sheds light on mycobacterial lipid metabolism and its regulation, and informs future anti-mycobacterial strategies.
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Metadata
- Authors
- Chen, Y., Wang, Y., & Chng, S.-S.
- Affiliations
- National University of Singapore (SG)
- Corresponding author
- Chng, Shu-Sin
- Venue
- Nature Communications
- Publisher
- openRxiv
- Published
- 2022-06-09
- Volume
- 14
- Issue
- 1
- Pages
- 5897-5897
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC10517005
- OpenAlex
- W4386944127
- Cited by
- 11
- References
- 1
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 1 · 2023: 1
- FWCI
- 2.27
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National University of Singapore
- Ministry of Education - Singapore (MOE2019-T2-1-128)
- Ministry of Education, India
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- Mycobacterium tuberculosis, Mycobacterium smegmatis, fatty acid uptake, ABC transporters, substrate-binding protein, membrane proteins, lipid metabolism, tuberculosis
- MeSH terms
- Membrane Proteins, Mycobacterium tuberculosis, ATP-Binding Cassette Transporters, Mycobacterium smegmatis, Membrane Transport Proteins
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