PDBsum entry 6feh

Metal transport

PDB id: 6feh

Contents

Protein chains

115 a.a.

148 a.a.

Metals

_CA ×4

References listed in PDB file

Key reference

• Title: Structural basis and energy landscape for the ca²⁺gating and calmodulation of the kv7.2 k⁺channel.
• Authors: G.Bernardo-Seisdedos, E.Nuñez, C.Gomis-Perez, C.Malo, �.�.Villarroel, O.Millet.
• Ref.: Proc Natl Acad Sci U S A, 2018, 115, 2395-2400.
• PubMed id: 29463698

Abstract

The Kv7.2 (KCNQ2) channel is the principal molecular component of the slow voltage-gated, noninactivating K⁺M-current, a key controller of neuronal excitability. To investigate the calmodulin (CaM)-mediated Ca²⁺gating of the channel, we used NMR spectroscopy to structurally and dynamically describe the association of heliceshA andhB of Kv7.2 with CaM, as a function of Ca²⁺concentration. The structures of the CaM/Kv7.2-hAB complex at two different calcification states are reported here. In the presence of a basal cytosolic Ca²⁺concentration (10-100 nM), only the N-lobe of CaM is Ca²⁺-loaded and the complex (representative of the open channel) exhibits collective dynamics on the millisecond time scale toward a low-populated excited state (1.5%) that corresponds to the inactive state of the channel. In response to a chemical or electrical signal, intracellular Ca²⁺levels rise up to 1-10 μM, triggering Ca²⁺association with the C-lobe. The associated conformational rearrangement is the key biological signal that shifts populations to the closed/inactive channel. This reorientation affects the C-lobe of CaM and both helices in Kv7.2, allosterically transducing the information from the Ca²⁺-binding site to the transmembrane region of the channel.