Molecular ruler mechanism and interfacial catalysis of the integral membrane acyltransferase PatA

[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 mann...

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Detalles Bibliográficos
Autores: Anso, Itxaso, Basso, Luis G. M., Wang, Lei, Marina, Alberto, Páez Pérez, Edgar D., Jager, Christian, Gavotto, Floriane, Tersa Peñacoba, Montserrat, Perrone, Sebastian, Contreras Gómez, Xabier, Prandi, Jacques, Gilleron, Martine, Linster, Carole L., Corzana, Francisco, Lowary, Todd L., Trastoy, Beatriz, Guerín, Marcelo Eduardo
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/54066
Acceso en línea:http://hdl.handle.net/10810/54066
Access Level:acceso abierto
Palabra clave:bacillus-calmette-guerin
phosphatidylinositol mannosides
mannosyltransferase pima
enzymatic acylation
structural basis
lipid-bilayer
biosynthesis
mycobacteria
recognition
dynamics
Descripción
Sumario:[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.

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