Serebryany Eugene, Folta-Stogniew Ewa, Liu Jian, Yan Elsa C Y
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.
W. M. Keck Foundation Biotechnology Resource Laboratory, Yale School of Medicine, Yale University, New Haven, CT, USA.
FEBS Lett. 2016 Dec;590(23):4308-4317. doi: 10.1002/1873-3468.12473. Epub 2016 Nov 19.
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.
配体结合中的协同性是蛋白质寡聚体的一个关键涌现特性。正协同性（对后续结合事件的亲和力高于初始结合）很常见。然而，代谢型谷氨酸受体1的对称同型二聚体配体结合结构域（LBD）表现出负协同性。为了研究其起源和功能意义，我们测量了野生型和C140S LBD在体外对谷氨酸的反应，该反应是二聚化程度的函数。我们的结果表明，相对于单体，同型二聚化增强了第一个而非第二个结合位点的亲和力，使二聚体受体具有更高的敏感性和更宽的动态范围。
