3bj4: Difference between revisions

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[[Image:3bj4.jpg|left|200px]]
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{{STRUCTURE_3bj4|  PDB=3bj4  |  SCENE=  }}  
{{STRUCTURE_3bj4|  PDB=3bj4  |  SCENE=  }}  


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




==Overview==
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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.
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==Disease==
==Disease==
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[[Category: Transport]]
[[Category: Transport]]
[[Category: Voltage-gated channel]]
[[Category: Voltage-gated channel]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 22:02:18 2008''

Revision as of 19:02, 2 July 2008

File:3bj4.png

Template:STRUCTURE 3bj4

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

Template:ABSTRACT PUBMED 18165683

Disease

Known disease associated with this structure: Atrial fibrillation, familial OMIM:[607542], Jervell and Lange-Nielsen syndrome OMIM:[607542], Long QT syndrome-1 OMIM:[607542], Short QT syndrome-2 OMIM:[607542], Torsades de pointes, drug-associated OMIM:[607542]

About this Structure

3BJ4 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

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

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