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Homodimerization enhances both sensitivity and dynamic range of the ligand‐binding domain of type 1 metabotropic glutamate receptor
Author(s) -
Serebryany Eugene,
FoltaStogniew Ewa,
Liu Jian,
Yan Elsa C. Y.
Publication year - 2016
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12473
Subject(s) - cooperativity , cooperative binding , metabotropic glutamate receptor , biophysics , chemistry , ligand (biochemistry) , metabotropic glutamate receptor 2 , metabotropic glutamate receptor 1 , metabotropic receptor , glutamate receptor , receptor , binding site , biochemistry , stereochemistry , biology
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.