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

Moolla, Nabiela and Bailo, Rebeca and Marshall, Robert and Bavro, Vassiliy N and Bhatt, Apoorva (2021) 'Structure-function analysis of MmpL7-mediated lipid transport in mycobacteria.' The Cell Surface, 7. p. 100062. ISSN 2468-2330

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: Mycobacterium tuberculosis; MmpL; PDIM; Lipid transport; RND transporters
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 13 Oct 2021 14:31
Last Modified: 06 Jan 2022 14:26
URI: http://repository.essex.ac.uk/id/eprint/31061

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