Nature Structural & Molecular Biology
- 13, 987 - 995 (2006)
Published online: 22 October 2006; | doi:10.1038/nsmb1164
Three-dimensional structure of the KChIP1–Kv4.3 T1 complex reveals a cross-shaped octamerMarta Pioletti1, 3, Felix Findeisen1, 3, Greg L Hura2 & Daniel L Minor, Jr11
Cardiovascular Research Institute, Departments of Biochemistry and Biophysics and Cellular and Molecular Pharmacology, California Institute for Quantitative Biomedical Research, University of California, San Francisco, California 94143-2532, USA. 2
Lawrence Berkeley National Laboratory, University of California, Berkeley, California 94720, USA. 3
These authors contributed equally to this work.
Correspondence should be addressed to Daniel L Minor, Jr daniel.minor@ucsf.edu Brain I
A and cardiac I
to currents arise from complexes containing Kv4 voltage-gated potassium channels and cytoplasmic calcium-sensor proteins (KChIPs). Here, we present X-ray crystallographic and small-angle X-ray scattering data that show that the KChIP1–Kv4.3 N-terminal cytoplasmic domain complex is a cross-shaped octamer bearing two principal interaction sites. Site 1 comprises interactions between a unique Kv4 channel N-terminal hydrophobic segment and a hydrophobic pocket formed by displacement of the KChIP H10 helix. Site 2 comprises interactions between a T1 assembly domain loop and the KChIP H2 helix. Functional and biochemical studies indicate that site 1 influences channel trafficking, whereas site 2 affects channel gating, and that calcium binding is intimately linked to KChIP folding and complex formation. Together, the data resolve how Kv4 channels and KChIPs interact and provide a framework for understanding how KChIPs modulate Kv4 function.
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