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

By Alvin C. Y. Kuk, E. Mashalidis, Seok-Yong Lee. 2016

77 citations recorded by the source corpus.

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. 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.

Subfields: Ecology, Genetics, Molecular Medicine

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In Ecology

1. Diego del Alamo
2. Jens Meiler
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4. Hassane S. Mchaourab

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1. Jens Meiler

Citations in the corpus

• Sampling alternative conformational states of transporters and receptors with AlphaFold2 (2022, background): “…the class A GPCR CCR5 ( Zheng et al., 2017 ; Zhang et al., 2021 ), the serotonin transporter SERT ( Coleman et al., 2016 ; Coleman et al., 2019 ), the multidrug transporter PfMATE ( Tanaka et al., 2013 ; Zakrzewska et al., 2019 ), and the lipid flippase MurJ ( Kuk et al., 2017 ; Kuk et al., 2019 ).”
• Inward-facing conformation of a multidrug resistance MATE family transporter (2019, background): “Among the MOP superfamily, the PfMATE vestibule rather resembles that of the MurJ lipid II flippase from the MVF family, which is predominantly cationic (16) (SI Appendix, Fig.”