PDBsum entry 4gow

Protein binding

PDB id: 4gow

Contents

Protein chains

142 a.a.

26 a.a.

Metals

_CA ×4

Waters ×18

PDB id:

4gow

Name:

Protein binding

Title:

Crystal structure of ca2+/cam:kv7.4 (kcnq4) b helix complex

Structure:

Calmodulin. Chain: d. Synonym: cam. Engineered: yes. Potassium voltage-gated channel subfamily kqt member 4. Chain: a. Fragment: unp residues 522-593. Synonym: kqt-like 4, potassium channel subunit alpha kvlqt4, voltage- gated potassium channel subunit kv7.4.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: calm1, calm, cam, cam1, calm2, cam2, camb, calm3, calml2, cam3, camc, camiii. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: kcnq4.

Resolution:

2.60Å R-factor: 0.238 R-free: 0.268

Authors:

Q.Xu,A.Chang,A.Tolia,D.L.Minor Jr.

Key ref:

Q.Xu et al. (2013). Structure of a Ca(2+)/CaM:Kv7.4 (KCNQ4) B-helix complex provides insight into M current modulation. J Mol Biol, 425, 378-394. PubMed id: 23178170

Date:

20-Aug-12 Release date: 12-Dec-12

Protein chain

P0DP23  (CALM1_HUMAN) -  Calmodulin-1 from Homo sapiens

Seq: 149 a.a.

Struc: 142 a.a.

Protein chain

P56696  (KCNQ4_HUMAN) -  Potassium voltage-gated channel subfamily KQT member 4 from Homo sapiens

Seq: 695 a.a.

Struc: 26 a.a.

J Mol Biol 425:378-394 (2013)

PubMed id: 23178170

Structure of a Ca(2+)/CaM:Kv7.4 (KCNQ4) B-helix complex provides insight into M current modulation.

Q.Xu, A.Chang, A.Tolia, D.L.Minor.

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.