title: A functional NMR for membrane proteins: dynamics, ligand binding, and allosteric modulation.
abstract: By nature of conducting ions, transporting substrates and transducing signals, membrane channels, transporters and receptors are expected to exhibit intrinsic conformational dynamics. It is therefore of great interest and importance to understand the various properties of conformational dynamics acquired by these proteins, for example, the relative population of states, exchange rate, conformations of multiple states, and how small molecule ligands modulate the conformational exchange. Because small molecule binding to membrane proteins can be weak and/or dynamic, structural characterization of these effects is very challenging. This review describes several NMR studies of membrane protein dynamics, ligand-induced conformational rearrangements, and the effect of ligand binding on the equilibrium of conformational exchange. The functional significance of the observed phenomena is discussed.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, 02115.
authors.forename: Kirill
authors.initials: K
authors.lastname: Oxenoid
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, 02115.
authors.forename: James J
authors.initials: JJ
authors.lastname: Chou
mesh_terms: D000494:Allosteric Regulation; D001665:Binding Sites; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D008024:Ligands; D008565:Membrane Proteins
keywords: NMR; allosteric modulation; drug binding; ion channels; membrane receptors; protein dynamics; transporters