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

Autor: Anso I; Structural Glycobiology Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 801A, 48160 Derio, Spain.; Structural Glycobiology Laboratory, Biocruces Bizkaia Health Research Institute, Cruces University Hospital, 48903 Barakaldo, Bizkaia, Spain., Basso LGM; Laboratório de Ciências Físicas, Centro de Ciência e Tecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Avenida Alberto Lamego, 2000, Campos dos Goytacazes, 28013-602 Rio de Janeiro, Brazil.; Laboratório de Biofísica Molecular, Departamento de Física, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes, 3900, 14040-901 Ribeirão Preto, São Paulo, Brazil., Wang L; Department of Chemistry, University of Alberta, Edmonton, Alberta, T6G 2G2, Canada., Marina A; Structural Glycobiology Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 801A, 48160 Derio, Spain., Páez-Pérez ED; Structural Glycobiology Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 801A, 48160 Derio, Spain.; IPICYT, División de Biología Molecular, Instituto Potosino de Investigación Científica y Tecnológica A.C., San Luis Potosí, México., Jäger C; Luxembourg Centre for Systems Biomedicine, University of Luxembourg, L-4367 Belvaux, Luxembourg., Gavotto F; Luxembourg Centre for Systems Biomedicine, University of Luxembourg, L-4367 Belvaux, Luxembourg., Tersa M; Structural Glycobiology Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 801A, 48160 Derio, Spain., Perrone S; Structural Glycobiology Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 801A, 48160 Derio, Spain.; Structural Glycobiology Laboratory, Biocruces Bizkaia Health Research Institute, Cruces University Hospital, 48903 Barakaldo, Bizkaia, Spain.; Luxembourg Centre for Systems Biomedicine, University of Luxembourg, L-4367 Belvaux, Luxembourg., Contreras FX; Instituto Biofisika, Consejo Superior de Investigaciones Científicas, Universidad del País Vasco/Euskal Herriko Unibertsitatea (CSIC,UPV/EHU), Barrio Sarriena s/n, Leioa, 48940 Bizkaia, Spain.; Departamento de Bioquímica, Universidad del País Vasco, Leioa, 48940 Bizkaia, Spain.; IKERBASQUE, Basque Foundation for Science, 48013 Bilbao, Spain., Prandi J; Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, 205 route de Narbonne, F-31077 Toulouse, France., Gilleron M; Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, 205 route de Narbonne, F-31077 Toulouse, France., Linster CL; Luxembourg Centre for Systems Biomedicine, University of Luxembourg, L-4367 Belvaux, Luxembourg., Corzana F; Departamento Química and Centro de Investigación en Síntesis Quı́mica, Universidad de La Rioja, 26006 Rioja, Spain., Lowary TL; Department of Chemistry, University of Alberta, Edmonton, Alberta, T6G 2G2, Canada.; Institute of Biological Chemistry, Academia Sinica, Academia Road, Section 2, #128, Nangang, Taipei 11529, Taiwan.; Institute of Biochemical Sciences, National Taiwan University, Section 4, #1, Roosevelt Road, Taipei 10617, Taiwan., Trastoy B; Structural Glycobiology Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 801A, 48160 Derio, Spain.; Structural Glycobiology Laboratory, Biocruces Bizkaia Health Research Institute, Cruces University Hospital, 48903 Barakaldo, Bizkaia, Spain., Guerin ME; Structural Glycobiology Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 801A, 48160 Derio, Spain.; Structural Glycobiology Laboratory, Biocruces Bizkaia Health Research Institute, Cruces University Hospital, 48903 Barakaldo, Bizkaia, Spain.; IKERBASQUE, Basque Foundation for Science, 48013 Bilbao, Spain.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2021 Oct 15; Vol. 7 (42), pp. eabj4565. Date of Electronic Publication: 2021 Oct 15.
DOI: 10.1126/sciadv.abj4565
Abstrakt: 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.
Databáze: MEDLINE