PDBsum entry 5j03

Transport protein

PDB id: 5j03

Contents

Protein chains

73 a.a.

146 a.a.

Ligands

ACT

Metals

_CA ×5

Waters ×133

PDB id:

5j03

Name:

Transport protein

Title:

Crystal structure of a chimeric kv7.2 - kv7.3 proximal c-terminal domain in complex with calmodulin

Structure:

Potassium voltage-gated channel subfamily kqt member 3, potassium voltage-gated channel subfamily kqt member 2. Chain: a. Synonym: kqt-like 3,potassium channel subunit alpha kvlqt3,voltage- gated potassium channel subunit kv7.3,kqt-like 2,neuroblastoma- specific potassium channel subunit alpha kvlqt2,voltage-gated potassium channel subunit kv7.2. Engineered: yes. Other_details: the sequence is chimeric. Residues 29-82 correspond to

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: kcnq3, kcnq2. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: calm1, calm, cam, cam1, calm2, cam2, camb, calm3, calml2, cam3, camc, camiii. Expression_system_taxid: 562

Resolution:

2.00Å R-factor: 0.181 R-free: 0.228

Authors:

R.Strulovich,J.A.Hirsch

Key ref:

R.Strulovich et al. (2016). Structural Insights into the M-Channel Proximal C-Terminus/Calmodulin Complex. Biochemistry, 55, 5353-5365. PubMed id: 27564677 DOI: 10.1021/acs.biochem.6b00477

Date:

26-Mar-16 Release date: 07-Sep-16

Protein chain

O43525  (KCNQ3_HUMAN) -  Potassium voltage-gated channel subfamily KQT member 3 from Homo sapiens

Seq: 872 a.a.

Struc: 73 a.a.*

Protein chain

P0DP23  (CALM1_HUMAN) -  Calmodulin-1 from Homo sapiens

Seq: 149 a.a.

Struc: 146 a.a.

* PDB and UniProt seqs differ at 24 residue positions (black crosses)

DOI no: 10.1021/acs.biochem.6b00477

Biochemistry 55:5353-5365 (2016)

PubMed id: 27564677

Structural Insights into the M-Channel Proximal C-Terminus/Calmodulin Complex.

R.Strulovich, W.S.Tobelaim, B.Attali, J.A.Hirsch.

ABSTRACT

The Kv7 (KCNQ) channel family, comprising voltage-gated potassium channels, plays major roles in fine-tuning cellular excitability by reducing firing frequency and controlling repolarization. Kv7 channels have a unique intracellular C-terminal (CT) domain bound constitutively by calmodulin (CaM). This domain plays key functions in channel tetramerization, trafficking, and gating. CaM binds to the proximal CT, comprising helices A and B. Kv7.2 and Kv7.3 are expressed in neural tissues. Together, they form the heterotetrameric M channel. We characterized Kv7.2, Kv7.3, and chimeric Kv7.3 helix A-Kv7.2 helix B (Q3A-Q2B) proximal CT/CaM complexes by solution methods at various Ca(2+)concentrations and determined them all to have a 1:1 stoichiometry. We then determined the crystal structure of the Q3A-Q2B/CaM complex at high Ca(2+) concentration to 2.0 Å resolution. CaM hugs the antiparallel coiled coil of helices A and B, braced together by an additional helix. The structure displays a hybrid apo-Ca(2+) CaM conformation even though four Ca(2+) ions are bound. Our results pinpoint unique interactions enabling the possible intersubunit pairing of Kv7.3 helix A and Kv7.2 helix B while underlining the potential importance of Kv7.3 helix A's role in stabilizing channel oligomerization. Also, the structure can be used to rationalize various channelopathic mutants. Functional testing of the chimeric channel found it to have a voltage-dependence similar to the M channel, thereby demonstrating helix A's importance in imparting gating properties.