5HIT

Crystal Structure Analysis of Ca2+-calmodulin and a C-terminal EAG1 channel fragment

Summary for 5HIT

• Entry DOI: 10.2210/pdb5hit/pdb
• Descriptor: Calmodulin, Potassium voltage-gated channel subfamily H member 1, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: calmodulin, potassium channel, signaling protein
• Biological source: Gallus gallus (Chicken); More
• Total number of polymer chains: 2
• Total formula weight: 18701.76

Authors

Marques-Carvalho, M.J.,Morais-Cabral, J.H. (deposition date: 2016-01-12, release date: 2016-09-14, Last modification date: 2024-01-10)

Primary citation

Marques-Carvalho, M.J.,Oppermann, J.,Munoz, E.,Fernandes, A.S.,Gabant, G.,Cadene, M.,Heinemann, S.H.,Schonherr, R.,Morais-Cabral, J.H.
Molecular Insights into the Mechanism of Calmodulin Inhibition of the EAG1 Potassium Channel.
Structure, 24:1742-1754, 2016

PubMed Abstract: The 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 Ca/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.

PubMed: 27618660
DOI: 10.1016/j.str.2016.07.020

Experimental method

X-RAY DIFFRACTION (2.85 Å)