4GOW

Crystal Structure of Ca2+/CaM:Kv7.4 (KCNQ4) B helix complex

4GOW の概要

• エントリーDOI: 10.2210/pdb4gow/pdb
• 分子名称: Calmodulin, Potassium voltage-gated channel subfamily KQT member 4, CALCIUM ION, ... (4 entities in total)
• 機能のキーワード: protein complex, protein binding, ion channel, calmodulin, potassium channel
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm, cytoskeleton, spindle: P62158; Basal cell membrane; Multi-pass membrane protein: P56696
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 24706.91

構造登録者

Xu, Q.,Chang, A.,Tolia, A.,Minor Jr., D.L. (登録日: 2012-08-20, 公開日: 2012-12-12, 最終更新日: 2024-02-28)

主引用文献

Xu, Q.,Chang, A.,Tolia, A.,Minor, D.L.
Structure of a Ca(2+)/CaM:Kv7.4 (KCNQ4) B-helix complex provides insight into M current modulation.
J.Mol.Biol., 425:378-394, 2013

PubMed Abstract: Calmodulin (CaM) is an important regulator of Kv7.x (KCNQx) voltage-gated potassium channels. Channels from this family produce neuronal M currents and cardiac and auditory I(KS) currents and harbor mutations that cause arrhythmias, epilepsy, and deafness. Despite extensive functional characterization, biochemical and structural details of the interaction between CaM and the channel have remained elusive. Here, we show that both apo-CaM and Ca(2+)/CaM bind to the C-terminal tail of the neuronal channel Kv7.4 (KCNQ4), which is involved in both hearing and mechanosensation. Interactions between apo-CaM and the Kv7.4 tail involve two C-terminal tail segments, known as the A and B segments, whereas the interaction between Ca(2+)/CaM and the Kv7.4 C-terminal tail requires only the B segment. Biochemical studies show that the calcium dependence of the CaM:B segment interaction is conserved in all Kv7 subtypes. X-ray crystallographic determination of the structure of the Ca(2+)/CaM:Kv7.4 B segment complex shows that Ca(2+)/CaM wraps around the Kv7.4 B segment, which forms an α-helix, in an antiparallel orientation that embodies a variation of the classic 1-14 Ca(2+)/CaM interaction motif. Taken together with the context of prior studies, our data suggest a model for modulation of neuronal Kv7 channels involving a calcium-dependent conformational switch from an apo-CaM form that bridges the A and B segments to a Ca(2+)/CaM form bound to the B-helix. The structure presented here also provides a context for a number of disease-causing mutations and for further dissection of the mechanisms by which CaM controls Kv7 function.

PubMed: 23178170
DOI: 10.1016/j.jmb.2012.11.023

実験手法

X-RAY DIFFRACTION (2.6 Å)