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Crystal Structure Analysis of Ca2+-calmodulin and a C-terminal EAG1 channel fragmentCrystal Structure Analysis of Ca2+-calmodulin and a C-terminal EAG1 channel fragment
Structural highlights
FunctionCALM_CHICK Calmodulin mediates the control of a large number of enzymes, ion channels and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number of protein kinases and phosphatases. Publication Abstract from PubMedThe human EAG1 potassium channel belongs to the superfamily of KCNH voltage-gated potassium channels that have roles in cardiac repolarization and neuronal excitability. EAG1 is strongly inhibited by Ca2+/calmodulin (CaM) through a mechanism that is not understood. We determined the binding properties of CaM with each one of three previously identified binding sites (BDN, BDC1, and BDC2), analyzed binding to protein stretches that include more than one site, and determined the effect of neighboring globular domains on the binding properties. The determination of the crystal structure of CaM bound to BDC2 shows the channel fragment interacting with only the C lobe of calmodulin and adopting an unusual bent conformation. Based on this structure and on a functional and biochemical analysis of mutants, we propose a model for the mechanism of inhibition whereby the local conformational change induced by CaM binding at BDC2 lies at the basis of channel modulation. Molecular Insights into the Mechanism of Calmodulin Inhibition of the EAG1 Potassium Channel.,Marques-Carvalho MJ, Oppermann J, Munoz E, Fernandes AS, Gabant G, Cadene M, Heinemann SH, Schonherr R, Morais-Cabral JH Structure. 2016 Sep 7. pii: S0969-2126(16)30234-9. doi:, 10.1016/j.str.2016.07.020. PMID:27618660[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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