Combining native and ‘omics’ mass spectrometry to identify endogenous ligands bound to membrane proteins

Accepted/In Press date: 25 March 2020

e-pub ahead of print date: 4 May 2020

Published date: May 2020

Additional Information: Funding Information: C.V.R. is funded by a Wellcome Trust Investigator Award (no. 104633/Z/14/Z), an European Research Council Advanced Grant ENABLE (no. 641317) and a Medical Research Council Programme grant (no. MR/N020413/1). M.L. is supported by an Ingvar Carlsson Award from the Swedish Foundation for Strategic Research and a KI Faculty-funded Career Position. For the provision of computational resources, we thank the HECBioSim Consortium (Engineering and Physical Sciences Research Council EPSRC grant no. EP/R029407/1), and The University of Southampton High Performance Computing Facilities, Iridis 4 and 5. This research was also supported by an EPSRC Institutional Sponsorship 2016 award (no. EP/P511377/1) to J.G. and C.V.R. C.V.R. and J.G. perform consultancy services for OMass Therapeutics Ltd, and H.-Y.Y. and I.L. are employees of that company. J.G. is a Junior Research Fellow at The Queen’s College, Oxford. We thank N. Housden and C. Kleanthous (University of Oxford) for providing purified OmpF and OBS1; S. Chandler, D. Cooper-Shepherd and J. Benesch (University of Oxford) for HSP 16.5 and 16.9; and V. Papadopoulos and C. Essagian (McGill University Health Center) for generously providing the plasmid for Rs TSPO; T. Alison (University of Canterbury, New Zealand), M. McDonough (University of Oxford) and C.-C. Su (Case Western Reserve University, USA) for helpful discussions with electron density fitting; S. Fantin and B. Ruotolo (University of Michigan) for insightful discussions regarding TSPO, as well as members of the Robinson, Benesch and Rauschenbach groups (University of Oxford), Thermo Fisher Scientific and OMass Therapeutics for many helpful discussions and support. Publisher Copyright: © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.

Keywords: Native mass spectrometry, Nativeomics, de-orphanisation, endogenous ligands, lipids, membrane proteins, protein-ligand binding, structural biology, top-down mass spectrometry

Local EPrints ID: 441237

URI: http://eprints.soton.ac.uk/id/eprint/441237

DOI: doi:10.1038/s41592-020-0821-0

ISSN: 1548-7091

PURE UUID: 74e054a2-b791-4b8b-9442-305f58b5e5da

ORCID for Syma Khalid: orcid.org/0000-0002-3694-5044

Date deposited: 05 Jun 2020 16:31

Last modified: 17 Mar 2024 05:36