Molecular ruler mechanism and interfacial catalysis of the integral membrane acyltransferase PatA
dc.contributor.author | Anso, Itxaso | |
dc.contributor.author | Basso, Luis G. M. | |
dc.contributor.author | Wang, Lei | |
dc.contributor.author | Marina, Alberto | |
dc.contributor.author | Páez Pérez, Edgar D. | |
dc.contributor.author | Jager, Christian | |
dc.contributor.author | Gavotto, Floriane | |
dc.contributor.author | Tersa Peñacoba, Montserrat | |
dc.contributor.author | Perrone, Sebastian | |
dc.contributor.author | Contreras Gómez, Xabier | |
dc.contributor.author | Prandi, Jacques | |
dc.contributor.author | Gilleron, Martine | |
dc.contributor.author | Linster, Carole L. | |
dc.contributor.author | Corzana, Francisco | |
dc.contributor.author | Lowary, Todd L. | |
dc.contributor.author | Trastoy, Beatriz | |
dc.contributor.author | Guerín, Marcelo Eduardo | |
dc.date.accessioned | 2021-11-25T08:39:02Z | |
dc.date.available | 2021-11-25T08:39:02Z | |
dc.date.issued | 2021-10 | |
dc.identifier.citation | Science Advances 7(42) : (2021) / Article ID eabj4565 | es_ES |
dc.identifier.issn | 2375-2548 | |
dc.identifier.uri | http://hdl.handle.net/10810/54066 | |
dc.description.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. | es_ES |
dc.description.sponsorship | This work was supported by the MINECO/FEDER EU contracts BFU201677427-C2-2-R, BFU2017-92223-EXP, PID2019-105649RB-I00, Severo Ochoa Excellence Accreditation SEV-2016-0644; the Basque Government contract KK-2019/00076; NIH R01AI149297 (to M.E.G.); the MINECO/FEDER EU contract BFU-2015-68981-P and the Basque Government (IT1264-19) (to F.-X.C.); MINECO/FEDER EU contract RTI2018-099592-B-C21 (to F.C.); the Canadian Glycomics Network Grant SD-1 (to T.L.L.). European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement no. 844905 (to B.T.); the Basque Government (to I.A.); CONACyT fellowship no. 291276 (to E.D.P.-P.). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | American Association for the Advancement of Science | es_ES |
dc.relation | info:eu-repo/grantAgreement/EC/H2020/844905 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/BFU201677427-C2-2-R | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/BFU2017-92223-EXP | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/PID2019-105649RB-I00 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/BFU-2015-68981-P | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/RTI2018-099592-B-C21 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/SEV-2016-0644 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/3.0/es/ | * |
dc.subject | bacillus-calmette-guerin | es_ES |
dc.subject | phosphatidylinositol mannosides | es_ES |
dc.subject | mannosyltransferase pima | es_ES |
dc.subject | enzymatic acylation | es_ES |
dc.subject | structural basis | es_ES |
dc.subject | lipid-bilayer | es_ES |
dc.subject | biosynthesis | es_ES |
dc.subject | mycobacteria | es_ES |
dc.subject | recognition | es_ES |
dc.subject | dynamics | es_ES |
dc.title | Molecular ruler mechanism and interfacial catalysis of the integral membrane acyltransferase PatA | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. 4.0 (CC BY-NC). | es_ES |
dc.rights.holder | Atribución-NoComercial 3.0 España | * |
dc.relation.publisherversion | https://www.science.org/doi/10.1126/sciadv.abj4565 | es_ES |
dc.identifier.doi | 10.1126/sciadv.abj4565 | |
dc.contributor.funder | European Commission | |
dc.departamentoes | Bioquímica y biología molecular | es_ES |
dc.departamentoeu | Biokimika eta biologia molekularra | es_ES |
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Except where otherwise noted, this item's license is described as © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. 4.0 (CC BY-NC).