Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41598-019-47159-8
Title: The MmpL3 interactome reveals a complex crosstalk between cell envelope biosynthesis and cell elongation and division in mycobacteria
Authors: Belardinelli, Juan Manuel
Stevens, Casey M
Li, Wei
Tan, Yong Zi 
Jones, Victoria
Mancia, Filippo
Zgurskaya, Helen I
Jackson, Mary
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
MYCOLIC ACID TRANSPORTER
MEMBRANE TRANSPORTER
OUTER-MEMBRANE
TREHALOSE MONOMYCOLATE
TUBERCULOSIS
WALL
IDENTIFICATION
SYSTEM
PROTEINS
GROWTH
Issue Date: 24-Jul-2019
Publisher: NATURE PUBLISHING GROUP
Citation: Belardinelli, Juan Manuel, Stevens, Casey M, Li, Wei, Tan, Yong Zi, Jones, Victoria, Mancia, Filippo, Zgurskaya, Helen I, Jackson, Mary (2019-07-24). The MmpL3 interactome reveals a complex crosstalk between cell envelope biosynthesis and cell elongation and division in mycobacteria. SCIENTIFIC REPORTS 9 (1). ScholarBank@NUS Repository. https://doi.org/10.1038/s41598-019-47159-8
Abstract: Integral membrane transporters of the Mycobacterial Membrane Protein Large (MmpL) family and their interactome play important roles in the synthesis and export of mycobacterial outer membrane lipids. Despite the current interest in the mycolic acid transporter, MmpL3, from the perspective of drug discovery, the nature and biological significance of its interactome remain largely unknown. We here report on a genome-wide screening by two-hybrid system for MmpL3 binding partners. While a surprisingly low number of proteins involved in mycolic acid biosynthesis was found to interact with MmpL3, numerous enzymes and transporters participating in the biogenesis of peptidoglycan, arabinogalactan and lipoglycans, and the cell division regulatory protein, CrgA, were identified among the hits. Surface plasmon resonance and co-immunoprecipitation independently confirmed physical interactions for three proteins in vitro and/or in vivo. Results are in line with the focal localization of MmpL3 at the poles and septum of actively-growing bacilli where the synthesis of all major constituents of the cell wall core are known to occur, and are further suggestive of a role for MmpL3 in the coordination of new cell wall deposition during cell septation and elongation. This novel aspect of the physiology of MmpL3 may contribute to the extreme vulnerability and high therapeutic potential of this transporter.
Source Title: SCIENTIFIC REPORTS
URI: https://scholarbank.nus.edu.sg/handle/10635/227207
ISSN: 20452322
DOI: 10.1038/s41598-019-47159-8
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