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.
Pioletti
Marta
M
Cardiovascular Research Institute, Department of Biochemistry, California Institute for Quantitative Biomedical Research, University of California, San Francisco, California 94143-2532, USA.
Findeisen
Felix
F
Hura
Greg L
GL
Minor
Daniel L
DL
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D018360:Crystallography, X-Ray; D006801:Humans; D015640:Ion Channel Gating; D051605:Kv Channel-Interacting Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008564:Membrane Potentials; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018408:Patch-Clamp Techniques; D011485:Protein Binding; D011487:Protein Conformation; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012542:Scattering, Radiation; D051672:Shal Potassium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014965:X-Rays; D014981:Xenopus
D051605:Kv Channel-Interacting Proteins; D011993:Recombinant Fusion Proteins; D051672:Shal Potassium Channels; D002118:Calcium