title: Homodimerization enhances both sensitivity and dynamic range of the ligand-binding domain of type 1 metabotropic glutamate receptor.
abstract: Cooperativity in ligand binding is a key emergent property of protein oligomers. Positive cooperativity (higher affinity for subsequent binding events than for initial binding) is frequent. However, the symmetrically homodimeric ligand-binding domain (LBD) of metabotropic glutamate receptor type 1 exhibits negative cooperativity. To investigate its origin and functional significance, we measured the response to glutamate in vitro of wild-type and C140S LBD as a function of the extent of dimerization. Our results indicate that homodimerization enhances the affinity of the first, but not the second, binding site, relative to the monomer, giving the dimeric receptor both greater sensitivity and a broader dynamic range.
authors: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.
authors: Eugene
authors: E
authors: Serebryany
authors: W. M. Keck Foundation Biotechnology Resource Laboratory, Yale School of Medicine, Yale University, New Haven, CT, USA.
authors: Ewa
authors: E
authors: Folta-Stogniew
authors: Department of Chemistry, Yale University, New Haven, CT, USA.
authors: Jian
authors: J
authors: Liu
authors: Department of Chemistry, Yale University, New Haven, CT, USA.
authors: Elsa C Y
authors: EC
authors: Yan
mesh_terms: D000818:Animals; D018698:Glutamic Acid / Q000494:pharmacology; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D009154:Mutation; D055503:Protein Multimerization / Q000187:drug effects; D020836:Protein Structure, Quaternary / Q000187:drug effects; D018094:Receptors, Metabotropic Glutamate / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D008024:Ligands; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D018698:Glutamic Acid
keywords: G-protein coupled receptor; cooperativity; ligand binding; light scattering; venus flytrap fold