PDBsum entry 4umo

Signaling protein

PDB id: 4umo

Contents

Protein chains

75 a.a.

96 a.a.

145 a.a.

Ligands

SCN

Metals

__K ×4

_CA ×4

Waters ×1

PDB id:

4umo

Name:

Signaling protein

Title:

Crystal structure of the kv7.1 proximal c-terminal domain in complex with calmodulin

Structure:

Potassium voltage-gated channel subfamily kqt member 1. Chain: a, b. Fragment: proximal c-terminal domain, residues 352-396,502-539. Synonym: kv7.1 channel, iks producing slow voltage-gated potassium channel subunit alpha kvlqt1, kqt-like 1, voltage-gated potassium channel subunit kv7.1. Engineered: yes. Mutation: yes. Calmodulin.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 511693.

Resolution:

3.00Å R-factor: 0.215 R-free: 0.247

Authors:

D.Sachyani,J.A.Hirsch

Key ref:

D.Sachyani et al. (2014). Structural basis of a Kv7.1 potassium channel gating module: studies of the intracellular c-terminal domain in complex with calmodulin. Structure, 22, 1582-1594. PubMed id: 25441029 DOI: 10.1016/j.str.2014.07.016

Date:

20-May-14 Release date: 05-Nov-14

Protein chain

P51787  (KCNQ1_HUMAN) -  Potassium voltage-gated channel subfamily KQT member 1 from Homo sapiens

Seq: 676 a.a.

Struc: 75 a.a.*

Protein chain

P51787  (KCNQ1_HUMAN) -  Potassium voltage-gated channel subfamily KQT member 1 from Homo sapiens

Seq: 676 a.a.

Struc: 96 a.a.*

Protein chains

P0DP23  (CALM1_HUMAN) -  Calmodulin-1 from Homo sapiens

Seq: 149 a.a.

Struc: 145 a.a.

* PDB and UniProt seqs differ at 71 residue positions (black crosses)

DOI no: 10.1016/j.str.2014.07.016

Structure 22:1582-1594 (2014)

PubMed id: 25441029

Structural basis of a Kv7.1 potassium channel gating module: studies of the intracellular c-terminal domain in complex with calmodulin.

D.Sachyani, M.Dvir, R.Strulovich, G.Tria, W.Tobelaim, A.Peretz, O.Pongs, D.Svergun, B.Attali, J.A.Hirsch.

ABSTRACT

Kv7 channels tune neuronal and cardiomyocyte excitability. In addition to the channel membrane domain, they also have a unique intracellular C-terminal (CT) domain, bound constitutively to calmodulin (CaM). This CT domain regulates gating and tetramerization. We investigated the structure of the membrane proximal CT module in complex with CaM by X-ray crystallography. The results show how the CaM intimately hugs a two-helical bundle, explaining many channelopathic mutations. Structure-based mutagenesis of this module in the context of concatemeric tetramer channels and functional analysis along with in vitro data lead us to propose that one CaM binds to one individual protomer, without crosslinking subunits and that this configuration is required for proper channel expression and function. Molecular modeling of the CT/CaM complex in conjunction with small-angle X-ray scattering suggests that the membrane proximal region, having a rigid lever arm, is a critical gating regulator.