Three-dimensional structure of the KChIP1–Kv4.3 T1 complex reveals a cross-shaped octamer
Copyright policy )Three-dimensional structure of the KChIP1–Kv4.3 T1 complex reveals a cross-shaped octamer
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.
- Lawrence Berkeley National Laboratory United States
- University of California, Berkeley United States
- University of California, San Francisco United States
- California Institute for Biomedical Research United States
- Cardiovascular Institute Hospital Japan
Models, Molecular, Binding Sites, Patch-Clamp Techniques, Protein Conformation, Recombinant Fusion Proteins, X-Rays, Xenopus, Molecular Sequence Data, Kv Channel-Interacting Proteins, Crystallography, X-Ray, Membrane Potentials, Rats, Shal Potassium Channels, Animals, Humans, Scattering, Radiation, Calcium, Amino Acid Sequence, Ion Channel Gating, Protein Binding
Models, Molecular, Binding Sites, Patch-Clamp Techniques, Protein Conformation, Recombinant Fusion Proteins, X-Rays, Xenopus, Molecular Sequence Data, Kv Channel-Interacting Proteins, Crystallography, X-Ray, Membrane Potentials, Rats, Shal Potassium Channels, Animals, Humans, Scattering, Radiation, Calcium, Amino Acid Sequence, Ion Channel Gating, Protein Binding
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