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Calmodulin Lobes Facilitate Dimerization And Activation Of Estrogen Receptor-Alpha, Zhigang Li, Yonghong Zhang, Andrew C. Hedman, James B. Ames, David B. Sacks

Chemistry Faculty Publications and Presentations

Estrogen receptor α (ER-α) is a nuclear hormone receptor that controls selected genes, thereby regulating proliferation and differentiation of target tissues, such as breast. Gene expression controlled by ER-α is modulated by Ca²⁺ via calmodulin (CaM). Here we present the NMR structure of Ca²⁺-CaM bound to two molecules of ER-α (residues 287–305). The two lobes of CaM bind to the same site on two separate ER-α molecules (residues 292, 296, 299, 302, and 303), which explains why CaM binds two molecules of ER-α in a 1:2 complex and stabilizes ER-α dimerization. Exposed glutamate residues in CaM (Glu-11, …