BibTex format
@article{Cioccolo:2024:10.1039/D4CB00110A,
author = {Cioccolo, S and Barritt, JD and Pollock, N and Hall, Z and Babuta, J and Sridhar, P and Just, A and Morgner, N and Dafforn, T and Gould, I and Byrne, B},
doi = {10.1039/D4CB00110A},
journal = {RSC Chemical Biology},
pages = {901--913},
title = {The mycobacterium lipid transporter MmpL3 is dimeric in detergent solution, SMALPs and reconstituted nanodiscs},
url = {http://dx.doi.org/10.1039/D4CB00110A},
volume = {5},
year = {2024}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - The mycobacterial membrane protein large 3 (MmpL3) transports key precursor lipids to the outer membrane of Mycobacterium species. Multiple structures of MmpL3 from both M. tuberculosis and M. smegmatis in various conformational states indicate that the protein is both structurally and functionally monomeric. However, most other resistance, nodulation and cell division (RND) transporters structurally characterised to date are either dimeric or trimeric. Here we present an in depth biophysical and computational analysis revealing that MmpL3 from M. smegmatis exists as a dimer in a variety of membrane mimetic systems (SMALPs, detergent-based solution and nanodiscs). Sucrose gradient separation of MmpL3 populations from M. smegmatis, reconstituted into nanodiscs, identified monomeric and dimeric populations of the protein using laser induced liquid bead ion desorption (LILBID), a native mass spectrometry technique. Preliminary cryo-EM analysis confirmed that MmpL3 forms physiological dimers. Untargeted lipidomics experiments on membrane protein co-purified lipids revealed PE and PG lipid classes were predominant. Molecular dynamics simulations, in the presence of physiologically-relevant lipid compositions revealed the likely dimer interface.
AU - Cioccolo,S
AU - Barritt,JD
AU - Pollock,N
AU - Hall,Z
AU - Babuta,J
AU - Sridhar,P
AU - Just,A
AU - Morgner,N
AU - Dafforn,T
AU - Gould,I
AU - Byrne,B
DO - 10.1039/D4CB00110A
EP - 913
PY - 2024///
SN - 2633-0679
SP - 901
TI - The mycobacterium lipid transporter MmpL3 is dimeric in detergent solution, SMALPs and reconstituted nanodiscs
T2 - RSC Chemical Biology
UR - http://dx.doi.org/10.1039/D4CB00110A
UR - https://pubs.rsc.org/en/Content/ArticleLanding/2024/CB/D4CB00110A
UR - http://hdl.handle.net/10044/1/113654
VL - 5
ER -