3BJ4

The KCNQ1 (Kv7.1) C-terminus, a multi-tiered scaffold for subunit assembly and protein interaction

Summary for 3BJ4

• Entry DOI: 10.2210/pdb3bj4/pdb
• Descriptor: Potassium voltage-gated channel subfamily KQT member 1, NICKEL (II) ION (3 entities in total)
• Functional Keywords: coiled coil, alternative splicing, deafness, disease mutation, glycoprotein, ion transport, ionic channel, long qt syndrome, membrane, phosphoprotein, polymorphism, potassium, potassium channel, potassium transport, short qt syndrome, transmembrane, transport, voltage-gated channel, signaling protein
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane; Multi-pass membrane protein: P51787
• Total number of polymer chains: 2
• Total formula weight: 10907.05

Authors

Wiener, R.,Hirsch, J.A. (deposition date: 2007-12-03, release date: 2008-01-15, Last modification date: 2024-03-13)

Primary citation

Wiener, R.,Haitin, Y.,Shamgar, L.,Fernandez-Alonso, M.C.,Martos, A.,Chomsky-Hecht, O.,Rivas, G.,Attali, B.,Hirsch, J.A.
The KCNQ1 (Kv7.1) COOH terminus, a multitiered scaffold for subunit assembly and protein interaction.
J.Biol.Chem., 283:5815-5830, 2008

PubMed Abstract: The Kv7 subfamily of voltage-dependent potassium channels, distinct from other subfamilies by dint of its large intracellular COOH terminus, acts to regulate excitability in cardiac and neuronal tissues. KCNQ1 (Kv7.1), the founding subfamily member, encodes a channel subunit directly implicated in genetic disorders, such as the long QT syndrome, a cardiac pathology responsible for arrhythmias. We have used a recombinant protein preparation of the COOH terminus to probe the structure and function of this domain and its individual modules. The COOH-terminal proximal half associates with one calmodulin constitutively bound to each subunit where calmodulin is critical for proper folding of the whole intracellular domain. The distal half directs tetramerization, employing tandem coiled-coils. The first coiled-coil complex is dimeric and undergoes concentration-dependent self-association to form a dimer of dimers. The outer coiled-coil is parallel tetrameric, the details of which have been elucidated based on 2.0 A crystallographic data. Both coiled-coils act in a coordinate fashion to mediate the formation and stabilization of the tetrameric distal half. Functional studies, including characterization of structure-based and long QT mutants, prove the requirement for both modules and point to complex roles for these modules, including folding, assembly, trafficking, and regulation.

PubMed: 18165683
DOI: 10.1074/jbc.M707541200

Experimental method

X-RAY DIFFRACTION (2 Å)