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.
Zhou
Wei
W
Division of Neuroscience, Baylor College of Medicine, Houston, TX 77030 USA.
Qian
Yan
Y
Kunjilwar
Kumud
K
Pfaffinger
Paul J
PJ
Choe
Senyon
S
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