6FEG

Solution Structure of CaM/Kv7.2-hAB Complex

Summary for 6FEG

• Entry DOI: 10.2210/pdb6feg/pdb
• Descriptor: Potassium voltage-gated channel subfamily KQT member 2,Potassium voltage-gated channel subfamily KQT member 2, Calmodulin-1, CALCIUM ION (3 entities in total)
• Functional Keywords: voltage-gated potassium channel, calmodulin, complex, transport, calcium-signalling, metal transport
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 30532.24

Authors

Bernardo-Seisdedos, G.,Villarroel, A.,Millet, O. (deposition date: 2018-01-02, release date: 2018-02-21, Last modification date: 2024-05-15)

Primary citation

Bernardo-Seisdedos, G.,Nunez, E.,Gomis, C.,Malo, C.,Villarroel, A.,Millet, O.
Structural basis and energy landscape for the Ca2+gating and calmodulation of the Kv7.2 K+channel.
Proc. Natl. Acad. Sci. U.S.A., 115:2395-2400, 2018

PubMed 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 Ca gating of the channel, we used NMR spectroscopy to structurally and dynamically describe the association of helices A and B of Kv7.2 with CaM, as a function of Ca 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 Ca concentration (10-100 nM), only the N-lobe of CaM is Ca-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 Ca levels rise up to 1-10 μM, triggering Ca 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 Ca-binding site to the transmembrane region of the channel.

PubMed: 29463698
DOI: 10.1073/pnas.1800235115

Experimental method

SOLUTION NMR