Pentameric Assembly of Potassium Channel Tetramerization Domain-Containing Protein 5

JOURNAL OF MOLECULAR BIOLOGY

卷:387

Article

Dementieva, Irina S.^1,2  Tereshko, Valentina³  McCrossan, Zoe A.^1,2  Araki, Daniel^1,2  Xu, Chen⁴  Grigorieff, Nikolaus^4,5  Goldstein, Steve A. N.^1,2 

[1] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA

[2] Univ Chicago, Inst Mol Pediat Sci, Chicago, IL 60637 USA

[3] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA

[4] Rosenstiel Basic Med Sci Res Ctr, Waltham, MA 02454 USA

[5] Brandeis Univ, Howard Hughes Med Inst, Waltham, MA 02454 USA

关键词: KCTD5;    BTB;    Kv channel;    T1 domain;    GRASP55;   

DOI  :  10.1016/j.jmb.2009.01.030

来源: Elsevier

【 摘 要 】

We report the X-ray crystal structure of human potassium channel tetramerization domain-containing protein 5 (KCTD5), the first member of the family to be so characterized. Four findings were unexpected. First, the structure reveals assemblies of five subunits while tetramers were anticipated; pentameric stoichiometry is observed also in solution by scanning transmission electron microscopy mass analysis and analytical ultracentrifugation. Second, the same BTB (bric-a-brac, tramtrack, broad. complex) domain surface mediates the assembly of five KCTD5 and four voltage-gated K+ (Kv) channel subunits; four amino acid differences appear crucial. Third, KCTD5 complexes have well-defined N- and C-terminal modules separated by a flexible linker that swivels by similar to 30 degrees; the C-module shows a new fold and is required to bind Golgi reassembly stacking protein 55 with similar to 1 mu M affinity, as judged by surface plasmon resonance and ultracentrifugation. Fourth, despite the homology reflected in its name, KCTD5 does not impact the operation of Kv4.2, Kv3.4, Kv2.1, or Kv1.2 channels. (C) 2009 Elsevier Ltd. All rights reserved.

【 授权许可】

Free