Structure-function analysis of MmpL7-mediated lipid transport in mycobacteria.

Autor: Moolla N; School of Biosciences and Institute of Microbiology and Infection, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK., Bailo R; School of Biosciences and Institute of Microbiology and Infection, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK., Marshall R; School of Biosciences and Institute of Microbiology and Infection, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK., Bavro VN; School of Life Sciences, University of Essex, Colchester CO4 3SQ, UK., Bhatt A; School of Biosciences and Institute of Microbiology and Infection, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
Jazyk: angličtina
Zdroj: Cell surface (Amsterdam, Netherlands) [Cell Surf] 2021 Aug 31; Vol. 7, pp. 100062. Date of Electronic Publication: 2021 Aug 31 (Print Publication: 2021).
DOI: 10.1016/j.tcsw.2021.100062
Abstrakt: Mycobacterial membrane protein Large (MmpL7) is a Resistance-Nodulation-Division (RND) family transporter required for the export of the virulence lipid, phthiocerol dimycocerosate (PDIM), in Mycobacterium tuberculosis . Using a null mutant of the related, vaccine strain Mycobacterium bovis BCG, we show that MmpL7 is also involved in the transport of the structurally related phenolic glycolipid (PGL), which is also produced by the hypervirulent M. tuberculosis strain HN878, but absent in M. tuberculosis H37Rv. Furthermore, we generated an in silico model of M. tuberculosis MmpL7 that revealed MmpL7 as a functional outlier within the MmpL-family, missing a canonical proton-relay signature sequence, suggesting that it employs a yet-unidentified mechanism for energy coupling for transport. In addition, our analysis demonstrates that the periplasmic porter domain 2 insert (PD2-insert), which doesn't share any recognisable homology, is highly alpha-helical in nature, suggesting an organisation similar to that seen in the hopanoid PD3/4 domains. Using the M. bovis BCG mmpL7 mutant for functional complementation with mutated alleles of mmpL7 , we were able to identify residues present in the transmembrane domains TM4 and TM10, and the PD2 domain insert that play a crucial role in PDIM transport, and in certain cases, biosynthesis of PDIM.
Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(© 2021 The Author(s).)
Databáze: MEDLINE
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