PDBsum entry 6b8q

Metal transport

PDB id: 6b8q

Contents

Protein chains

62 a.a.

146 a.a.

66 a.a.

Metals

_MG ×15

Waters ×25

PDB id:

6b8q

Name:

Metal transport

Title:

Crystal structure of the mg2+/cam:kv7.5 (kcnq5) ab domain complex

Structure:

Potassium voltage-gated channel subfamily kqt member 5. Chain: a, c, e, g. Engineered: yes. Calmodulin-1. Chain: b, d, f, h. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: kcnq5. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: calm1, calm, cam, cam1.

Resolution:

2.60Å R-factor: 0.225 R-free: 0.270

Authors:

A.Chang,F.Abderemane-Ali,D.L.Minor

Key ref:

A.Chang et al. (2018). A Calmodulin C-Lobe Ca²⁺-Dependent Switch Governs Kv7 Channel Function. Neuron, 97, 836. PubMed id: 29429937

Date:

09-Oct-17 Release date: 14-Mar-18

Protein chains

Q9NR82  (KCNQ5_HUMAN) -  Potassium voltage-gated channel subfamily KQT member 5 from Homo sapiens

Seq: 932 a.a.

Struc: 62 a.a.*

Protein chains

P0DP23  (CALM1_HUMAN) -  Calmodulin-1 from Homo sapiens

Seq: 149 a.a.

Struc: 146 a.a.

Protein chain

Q9NR82  (KCNQ5_HUMAN) -  Potassium voltage-gated channel subfamily KQT member 5 from Homo sapiens

Seq: 932 a.a.

Struc: 66 a.a.*

* PDB and UniProt seqs differ at 64 residue positions (black crosses)

Neuron 97:836 (2018)

PubMed id: 29429937

A Calmodulin C-Lobe Ca²⁺-Dependent Switch Governs Kv7 Channel Function.

A.Chang, F.Abderemane-Ali, G.L.Hura, N.D.Rossen, R.E.Gate, D.L.Minor.

ABSTRACT

Kv7 (KCNQ) voltage-gated potassium channels control excitability in the brain, heart, and ear. Calmodulin (CaM) is crucial for Kv7 function, but how this calcium sensor affects activity has remained unclear. Here, we present X-ray crystallographic analysis of CaM:Kv7.4 and CaM:Kv7.5 AB domain complexes that reveal an Apo/CaM clamp conformation and calcium binding preferences. These structures, combined with small-angle X-ray scattering, biochemical, and functional studies, establish a regulatory mechanism for Kv7 CaM modulation based on a common architecture in which a CaM C-lobe calcium-dependent switch releases a shared Apo/CaM clamp conformation. This C-lobe switch inhibits voltage-dependent activation of Kv7.4 and Kv7.5 but facilitates Kv7.1, demonstrating that mechanism is shared by Kv7 isoforms despite the different directions of CaM modulation. Our findings provide a unified framework for understanding how CaM controls different Kv7 isoforms and highlight the role of membrane proximal domains for controlling voltage-gated channel function. VIDEO ABSTRACT.