Crystal structure of the MOP flippase MurJ in an inward-facing conformation
Abstract
Peptidoglycan (PG) protects bacteria from osmotic lysis, and its biogenesis is a key antibiotic target. A central step in PG biosynthesis is flipping of the lipid-linked PG precursor lipid II across the cytoplasmic membrane for subsequent incorporation into PG. MurJ, part of the multidrug/oligosaccharidyl-lipid/polysaccharide (MOP) transporter superfamily, was recently shown to carry out this process. However, understanding of how MurJ flips lipid II, and of how MOP transporters operate in general, remains limited due to a lack of structural information. Here we present a crystal structure of MurJ from Thermosipho africanus in an inward-facing conformation at 2.0-Å resolution. We report a hydrophobic groove is formed by two C-terminal transmembrane helices, which leads into a large central cavity that is mostly cationic. Our studies not only provide the first structural glimpse of MurJ but also suggest that alternating access is important for MurJ function, which may be applicable to other MOP superfamily transporters.
- Authors:
-
- Duke Univ. School of Medicine, Durham, NC (United States)
- Publication Date:
- Research Org.:
- Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Org.:
- Duke Startup Funds
- OSTI Identifier:
- 1356413
- Grant/Contract Number:
- P41GM103403; S10 RR029205
- Resource Type:
- Journal Article: Accepted Manuscript
- Journal Name:
- Nature Structural & Molecular Biology
- Additional Journal Information:
- Journal Volume: 24; Journal Issue: 2; Journal ID: ISSN 1545-9993
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Cellular microbiology; Membrane biophysics; Membrane proteins; X-ray crystallography
Citation Formats
Kuk, Alvin C. Y., Mashalidis, Ellene H., and Lee, Seok-Yong. Crystal structure of the MOP flippase MurJ in an inward-facing conformation. United States: N. p., 2016.
Web. doi:10.1038/nsmb.3346.
Kuk, Alvin C. Y., Mashalidis, Ellene H., & Lee, Seok-Yong. Crystal structure of the MOP flippase MurJ in an inward-facing conformation. United States. https://doi.org/10.1038/nsmb.3346
Kuk, Alvin C. Y., Mashalidis, Ellene H., and Lee, Seok-Yong. 2016.
"Crystal structure of the MOP flippase MurJ in an inward-facing conformation". United States. https://doi.org/10.1038/nsmb.3346. https://www.osti.gov/servlets/purl/1356413.
@article{osti_1356413,
title = {Crystal structure of the MOP flippase MurJ in an inward-facing conformation},
author = {Kuk, Alvin C. Y. and Mashalidis, Ellene H. and Lee, Seok-Yong},
abstractNote = {Peptidoglycan (PG) protects bacteria from osmotic lysis, and its biogenesis is a key antibiotic target. A central step in PG biosynthesis is flipping of the lipid-linked PG precursor lipid II across the cytoplasmic membrane for subsequent incorporation into PG. MurJ, part of the multidrug/oligosaccharidyl-lipid/polysaccharide (MOP) transporter superfamily, was recently shown to carry out this process. However, understanding of how MurJ flips lipid II, and of how MOP transporters operate in general, remains limited due to a lack of structural information. Here we present a crystal structure of MurJ from Thermosipho africanus in an inward-facing conformation at 2.0-Å resolution. We report a hydrophobic groove is formed by two C-terminal transmembrane helices, which leads into a large central cavity that is mostly cationic. Our studies not only provide the first structural glimpse of MurJ but also suggest that alternating access is important for MurJ function, which may be applicable to other MOP superfamily transporters.},
doi = {10.1038/nsmb.3346},
url = {https://www.osti.gov/biblio/1356413},
journal = {Nature Structural & Molecular Biology},
issn = {1545-9993},
number = 2,
volume = 24,
place = {United States},
year = {Mon Dec 26 00:00:00 EST 2016},
month = {Mon Dec 26 00:00:00 EST 2016}
}
Web of Science
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