Crystal structure of the MOP flippase MurJ in an inward-facing conformation

Kuk, Alvin C. Y.; Mashalidis, Ellene H.; Lee, Seok-Yong

doi:10.1038/nsmb.3346

Title: Crystal structure of the MOP flippase MurJ in an inward-facing conformation

Journal Article · Mon Dec 26 00:00:00 EST 2016 · Nature Structural & Molecular Biology

DOI:https://doi.org/10.1038/nsmb.3346· OSTI ID:1356413

Kuk, Alvin C. Y. ^[1]; Mashalidis, Ellene H. ^[1]; Lee, Seok-Yong ^[1]

Duke Univ. School of Medicine, Durham, NC (United States)

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.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: Duke Startup Funds

Grant/Contract Number:: P41GM103403; S10 RR029205

OSTI ID:: 1356413

Journal Information:: Nature Structural & Molecular Biology, Vol. 24, Issue 2; ISSN 1545-9993

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 54 works

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