title: High-resolution mass spectrometry of small molecules bound to membrane proteins.
abstract: Small molecules are known to stabilize membrane proteins and to modulate their function and oligomeric state, but such interactions are often hard to precisely define. Here we develop and apply a high-resolution, Orbitrap mass spectrometry-based method for analyzing intact membrane protein-ligand complexes. Using this platform, we resolve the complexity of multiple binding events, quantify small molecule binding and reveal selectivity for endogenous lipids that differ only in acyl chain length.
authors.affiliation: Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, UK.
authors.forename: Joseph
authors.identifier: http://orcid.org/0000-0001-7686-2983
authors.initials: J
authors.lastname: Gault
authors.affiliation: Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, UK.
authors.forename: Joseph A C
authors.initials: JA
authors.lastname: Donlan
authors.affiliation: Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, UK.
authors.forename: Idlir
authors.initials: I
authors.lastname: Liko
authors.affiliation: Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, UK.
authors.forename: Jonathan T S
authors.initials: JT
authors.lastname: Hopper
authors.affiliation: Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, UK.
authors.forename: Kallol
authors.initials: K
authors.lastname: Gupta
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, UK.
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Housden
authors.affiliation: Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, UK.
authors.forename: Weston B
authors.initials: WB
authors.lastname: Struwe
authors.affiliation: Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, UK.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Marty
authors.affiliation: Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, UK.
authors.forename: Todd
authors.initials: T
authors.lastname: Mize
authors.affiliation: Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, UK.
authors.forename: Cherine
authors.initials: C
authors.lastname: Bechara
authors.affiliation: CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Pudong, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Pudong, China.
authors.forename: Beili
authors.initials: B
authors.lastname: Wu
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, UK.
authors.forename: Colin
authors.initials: C
authors.lastname: Kleanthous
authors.affiliation: Thermo Fisher Scientific, Bremen, Germany.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Belov
authors.affiliation: Thermo Fisher Scientific, Bremen, Germany.
authors.forename: Eugen
authors.initials: E
authors.lastname: Damoc
authors.affiliation: Thermo Fisher Scientific, Bremen, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Makarov
authors.affiliation: Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, UK.
authors.forename: Carol V
authors.initials: CV
authors.lastname: Robinson
mesh_terms: D006801:Humans; D008055:Lipids / Q000737:chemistry*; D013058:Mass Spectrometry / Q000379:methods*; D008565:Membrane Proteins / Q000378:metabolism*; D008958:Models, Molecular; D010446:Peptide Fragments / Q000378:metabolism*; D011485:Protein Binding; D054852:Small Molecule Libraries / Q000378:metabolism*
chemical_list: D008055:Lipids; D008565:Membrane Proteins; D010446:Peptide Fragments; D054852:Small Molecule Libraries