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

DOI: 10.1126/sciadv.abj4565 DOI Help

Authors: Itxaso Anso (Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA); Cruces University Hospital) , Luis G. M. Basso (Universidade Estadual do Norte Fluminense Darcy Ribeiro; Universidade de São Paulo) , Lei Wang (University of Alberta) , Alberto Marina (Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA)) , Edgar D. Páez-Pérez (Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA); Instituto Potosino de Investigación Científica y Tecnológica) , Christian Jäger (University of Luxembourg) , Floriane Gavotto (University of Luxembourg) , Montse Tersa (Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA)) , Sebastian Perrone (Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA); Cruces University Hospital; University of Luxembourg) , F.-Xabier Contreras (Universidad del País Vasco/Euskal Herriko Unibertsitatea (CSIC,UPV/EHU); Universidad del País Vasco; IKERBASQUE, Basque Foundation for Science) , Jacques Prandi (Université de Toulouse, CNRS, UPS) , Martine Gilleron (Université de Toulouse, CNRS, UPS) , Carole L. Linster (University of Luxembourg) , Francisco Corzana (Universidad de La Rioja) , Todd L. Lowary (University of Alberta; Institute of Biological Chemistry, Academia Sinica; National Taiwan University) , Beatriz Trastoy (Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA); Cruces University Hospital) , Marcelo E. Guerin (Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA); Cruces University Hospital; IKERBASQUE)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Science Advances , VOL 7

State: Published (Approved)
Published: October 2021
Diamond Proposal Number(s): 20113

Open Access Open Access

Abstract: 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.

Diamond Keywords: Tuberculosis (TB); Bacteria; Enzymes

Subject Areas: Biology and Bio-materials, Chemistry


Instruments: I03-Macromolecular Crystallography

Other Facilities: BL13-XALOC at ALBA

Added On: 22/10/2021 09:32

Discipline Tags:

Catalysis Life Sciences & Biotech Biophysics Health & Wellbeing Infectious Diseases Pathogens Structural biology Chemistry Biochemistry

Technical Tags:

Diffraction Macromolecular Crystallography (MX)