Article (Scientific journals)
Molecular ruler mechanism and interfacial catalysis of the integral membrane acyltransferase PatA
Anso, Itxaso; Basso, Luis G. M.; Wang, Lei et al.
2021In Science Advances, 7 (42)
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Abstract :
[en] Glycolipids are prominent components of bacterial membranes that play critical roles not only in maintaining the structural integrity of the cell but also in modulating host-pathogen interactions. PatA is an essential acyltransferase involved in the biosynthesis of phosphatidyl-myo-inositol mannosides (PIMs), key structural elements and virulence factors of Mycobacterium tuberculosis. We demonstrate by electron spin resonance spectroscopy and surface plasmon resonance that PatA is an integral membrane acyltransferase tightly anchored to anionic lipid bilayers, using a two-helix structural motif and electrostatic interactions. PatA dictates the acyl chain composition of the glycolipid by using an acyl chain selectivity “ruler.” We established this by a combination of structural biology, enzymatic activity, and binding measurements on chemically synthesized nonhydrolyzable acyl–coenzyme A (CoA) derivatives. We propose an interfacial catalytic mechanism that allows PatA to acylate hydrophobic PIMs anchored in the inner membrane of mycobacteria, through the use of water-soluble acyl-CoA donors.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Anso, Itxaso
Basso, Luis G. M.
Wang, Lei
Marina, Alberto
Páez-Pérez, Edgar D.
Jäger, Christian  ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Scientific Central Services
gavotto, Floriane ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Scientific Central Services
Tersa, Montse
Perrone, Sebastian ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Enzymology and Metabolism
Contreras, F.-Xabier
Prandi, Jacques
Gilleron, Martine
Linster, Carole  ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Enzymology and Metabolism
Corzana, Francisco
Lowary, Todd L.
Trastoy, Beatriz
Guerin, Marcelo E.
More authors (7 more) Less
External co-authors :
yes
Language :
English
Title :
Molecular ruler mechanism and interfacial catalysis of the integral membrane acyltransferase PatA
Publication date :
2021
Journal title :
Science Advances
ISSN :
2375-2548
Publisher :
American Association for the Advancement of Science (AAAS), Washington, United States - District of Columbia
Volume :
7
Issue :
42
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBilu :
since 17 November 2021

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