4V0C

Crystal Structure of the Kv7.1 proximal C-terminal Domain in Complex with Calmodulin

Summary for 4V0C

• Entry DOI: 10.2210/pdb4v0c/pdb
• Descriptor: POTASSIUM VOLTAGE-GATED CHANNEL SUBFAMILY KQT MEMBER 1, CALMODULIN, THIOCYANATE ION, ... (5 entities in total)
• Functional Keywords: signaling protein, voltage-dependent potassium channels, long qt syndrome, calmodulin
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Cell membrane ; Multi-pass membrane protein : P51787; Cytoplasm, cytoskeleton, spindle : P62158
• Total number of polymer chains: 4
• Total formula weight: 60899.99

Authors

Sachyani, D.,Hirsch, J.A. (deposition date: 2014-09-14, release date: 2014-11-05, Last modification date: 2024-05-08)

Primary citation

Sachyani, D.,Dvir, M.,Strulovich, R.,Tria, G.,Tobelaim, W.,Peretz, A.,Pongs, O.,Svergun, D.,Attali, B.,Hirsch, J.A.
Structural Basis of a Kv7.1 Potassium Channel Gating Module: Studies of the Intracellular C-Terminal Domain in Complex with Calmodulin.
Structure, 22:1582-, 2014

PubMed Abstract: Kv7 channels tune neuronal and cardiomyocyte excitability. In addition to the channel membrane domain, they also have a unique intracellular C-terminal (CT) domain, bound constitutively to calmodulin (CaM). This CT domain regulates gating and tetramerization. We investigated the structure of the membrane proximal CT module in complex with CaM by X-ray crystallography. The results show how the CaM intimately hugs a two-helical bundle, explaining many channelopathic mutations. Structure-based mutagenesis of this module in the context of concatemeric tetramer channels and functional analysis along with in vitro data lead us to propose that one CaM binds to one individual protomer, without crosslinking subunits and that this configuration is required for proper channel expression and function. Molecular modeling of the CT/CaM complex in conjunction with small-angle X-ray scattering suggests that the membrane proximal region, having a rigid lever arm, is a critical gating regulator.

PubMed: 25441029
DOI: 10.1016/J.STR.2014.07.016

Experimental method

X-RAY DIFFRACTION (2.86 Å)