Structural insights into the functional interaction of KChIP1 with Shal-type K(+) channels.
Four Kv channel-interacting proteins (KChIP1 through KChIP4) interact directly with the N-terminal domain of three Shal-type voltage-gated potassium channels (Kv4.1, Kv4.2, and Kv4.3) to modulate cell surface expression and function of Kv4 channels. Here we report a 2.0 Angstrom crystal structure of the core domain of KChIP1 (KChIP1*) in complex with the N-terminal fragment of Kv4.2 (Kv4.2N30). The complex reveals a clam-shaped dimeric assembly. Four EF-hands from each KChIP1 form each shell of the clam. The N-terminal end of Kv4.2 forming an alpha helix (alpha1) and the C-terminal alpha helix (H10) of KChIP1 are enclosed nearly coaxially by these shells. As a result, the H10 of KChIP1 and alpha1 of Kv4.2 mediate interactions between these two molecules, structurally reminiscent of the interactions between calmodulin and its target peptides. Site-specific mutagenesis combined with functional characterization shows that those interactions mediated by alpha1 and H10 are essential to the modulation of Kv4.2 by KChIPs.
Division of Neuroscience, Baylor College of Medicine, Houston, TX 77030 USA.
Wei
W
Zhou
Yan
Y
Qian
Kumud
K
Kunjilwar
Paul J
PJ
Pfaffinger
Senyon
S
Choe
D000818:Animals; D001665:Binding Sites / Q000235:genetics; D016466:CHO Cells; D019556:COS Cells; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006224:Cricetinae; D018360:Crystallography, X-Ray; D019281:Dimerization; D051605:Kv Channel-Interacting Proteins; D008564:Membrane Potentials / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed / Q000235:genetics; D010649:Phenylalanine / Q000378:metabolism; D015221:Potassium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated; D017433:Protein Structure, Secondary / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017386:Sequence Homology, Amino Acid; D051672:Shal Potassium Channels; D014364:Tryptophan / Q000378:metabolism
D002135:Calcium-Binding Proteins; C497017:Kcnd1 protein, rat; C497020:Kcnd2 protein, rat; C496757:Kcnip1 protein, rat; D051605:Kv Channel-Interacting Proteins; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D021122:Protein Subunits; D051672:Shal Potassium Channels; D010649:Phenylalanine; D014364:Tryptophan; D002118:Calcium