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TitleMprF from is a promiscuous lipid scramblase with broad substrate specificity.
Journal, issue, pagesSci Adv, Vol. 11, Issue 15, Page eads9135, Year 2025
Publish dateApr 11, 2025
AuthorsMatthew T K Hankins / Matyas Parrag / Alisa A Garaeva / Jennifer C Earp / Markus A Seeger / Phillip J Stansfeld / Maike Bublitz /
PubMed AbstractThe multiple peptide resistance factor (MprF) is a bifunctional membrane protein found in many bacteria, including and . MprF modifies inner leaflet lipid headgroups through aminoacylation and ...The multiple peptide resistance factor (MprF) is a bifunctional membrane protein found in many bacteria, including and . MprF modifies inner leaflet lipid headgroups through aminoacylation and translocates modified lipid to the outer leaflet. This activity provides increased resistance to antimicrobial agents. MprF presents a promising target in multiresistant pathogens, but structural information is limited and both substrate specificity and energization of MprF-mediated lipid transport are poorly understood. Here, we present the cryo-EM structure of MprF from (MprF) bound to a synthetic nanobody. MprF adopts an "open" conformation with a wide, lipid-exposed groove on the periplasmic side that induces a local membrane deformation in molecular dynamics simulations. Using an in vitro liposome transport assay, we demonstrate that MprF translocates a wide range of different lipids without an external energy source. This suggests that MprF is the first dedicated lipid scramblase to be characterized in bacteria.
External linksSci Adv / PubMed:40203087 / PubMed Central
MethodsEM (single particle)
Resolution3.28 Å
Structure data

51497

9goe

EMDB-51497, PDB-9goe:
Cryo-EM structure of the multiple peptide resistance factor (MprF) from Pseudomonas aeruginosa bound to a synthetic nanobody (Sb29)
Method: EM (single particle) / Resolution: 3.28 Å

Source
  • pseudomonas aeruginosa pao1 (bacteria)
  • synthetic construct (others)
KeywordsMEMBRANE PROTEIN / Lipid Transport / Sybody complex / Antimicrobial Resistance / Saposin-protein Nanoparticle

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