3bj4
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The KCNQ1 (Kv7.1) C-terminus, a multi-tiered scaffold for subunit assembly and protein interaction
OverviewOverview
The Kv7 subfamily of voltage-dependent potassium channels, distinct from, other subfamilies by dint of its large intracellular C-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 (LQT) syndrome, a cardiac, pathology responsible for arrhythmias. We have used a recombinant protein, preparation of the C-terminus to probe the structure and function of this, domain and its individual modules. The C-terminus proximal half associates, with one calmodulin (CaM) constitutively bound to each subunit where CaM, 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 that undergoes, concentration-dependent self-association to form a dimer of dimers. The, outer coiled-coil is parallel tetrameric, whose details 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 LQT mutants prove the requirement for both modules and, point to complex roles for these modules including folding, assembly, trafficking and regulation.
About this StructureAbout this Structure
3BJ4 is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
ReferenceReference
The KCNQ1 (Kv7.1) C-terminus, a multi-tieredscaffold for subunit assembly and protein interaction., Wiener R, Haitin Y, Shamgar L, Fernandez-Alonso MC, Martos A, Chomsky-Hecht O, Rivas G, Attali B, Hirsch JA, J Biol Chem. 2007 Dec 29;. PMID:18165683
Page seeded by OCA on Wed Jan 23 11:11:41 2008
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- Homo sapiens
- Single protein
- Hirsch, J.A.
- Wiener, R.
- NI
- Alternative splicing
- Coiled coil
- Deafness
- Disease mutation
- Glycoprotein
- Ion transport
- Ionic channel
- Long qt syndrome
- Membrane
- Phosphoprotein
- Polymorphism
- Potassium
- Potassium channel
- Potassium transport
- Short qt syndrome
- Signaling protein
- Transmembrane
- Transport
- Voltage-gated channel