Calmodulin Lobes Facilitate Dimerization and Activation of Estrogen Receptor-α.

ABSTRACT: 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, Glu-14, Glu-84, and Glu-87) form salt bridges with key lysine residues in ER-α (Lys-299, Lys-302, and Lys-303), which is likely to prevent ubiquitination at these sites

SUBMITTER: Li Z 

PROVIDER: S-EPMC5377777 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature