Two N-terminal domains of Kv4 K(+) channels regulate binding to and modulation by KChIP1.
The family of calcium binding proteins called KChIPs associates with Kv4 family K(+) channels and modulates their biophysical properties. Here, using mutagenesis and X-ray crystallography, we explore the interaction between Kv4 subunits and KChIP1. Two regions in the Kv4.2 N terminus, residues 7-11 and 71-90, are necessary for KChIP1 modulation and interaction with Kv4.2. When inserted into the Kv1.2 N terminus, residues 71-90 of Kv4.2 are also sufficient to confer association with KChIP1. To provide a structural framework for these data, we solved the crystal structures of Kv4.3N and KChIP1 individually. Taken together with the mutagenesis data, the individual structures suggest that that the Kv4 N terminus is required for stable association with KChIP1, perhaps through a hydrophobic surface interaction, and that residues 71-90 in Kv4 subunits form a contact loop that mediates the specific association of KChIPs with Kv4 subunits.
Neuroscience Discovery Research, Wyeth Research CN-8000, Princeton, NJ 08543, USA.
Robert H
RH
Scannevin
KeWei
K
Wang
Flora
F
Jow
Jennifer
J
Megules
David C
DC
Kopsco
Wade
W
Edris
Karen C
KC
Carroll
Qiang
Q
Lü
Weixin
W
Xu
Zhangbao
Z
Xu
Alan H
AH
Katz
Stephane
S
Olland
Laura
L
Lin
Meggin
M
Taylor
Mark
M
Stahl
Karl
K
Malakian
Will
W
Somers
Lydia
L
Mosyak
Mark R
MR
Bowlby
Pranab
P
Chanda
Kenneth J
KJ
Rhodes
D000595:Amino Acid Sequence / Q000502:physiology; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D006801:Humans; D051605:Kv Channel-Interacting Proteins; D008564:Membrane Potentials / Q000235:genetics; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed / Q000235:genetics; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D021122:Protein Subunits; D051672:Shal Potassium Channels
D002135:Calcium-Binding Proteins; C497018:KCND2 protein, human; C496750:KCNIP1 protein, human; D051605:Kv Channel-Interacting Proteins; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D021122:Protein Subunits; D051672:Shal Potassium Channels