Channelpedia

PubMed 26148514


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: KCNQ2 , Kv7.2 , SK2



Title: An unconventional calmodulin-anchoring site within the AB module of Kv7.2 channels.

Authors: Carolina Gomis-Perez, Alessandro Alaimo, Juncal Fernández-Orth, Araitz Alberdi, Paloma Aivar-Mateo, Ganeko Bernardo-Seisdedos, Covadonga Malo, Pilar Areso, Antonio Felipe, Alvaro Villarroel

Journal, date & volume: J. Cell. Sci., 2015 Aug 15 , 128, 3155-63

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/26148514


Abstract
Calmodulin (CaM) binding to the AB module is crucial for multiple mechanisms governing the function of Kv7.2 (also known as KCNQ2) K(+) channel subunits, which mediate one of the main components of the non-inactivating K(+) M-current, a key controller of neuronal excitability. Structural analysis indicates that the CaM N-lobe engages with helix B, whereas the C-lobe anchors to the IQ site within helix A. Here, we report the identification of a new site between helices A and B that assists in CaM binding whose sequence is reminiscent of the TW helix within the CaM C-lobe anchoring site of SK2 K(+) channels (also known as KCNN2). Mutations that disrupt CaM binding within the TW site, helix B or helix A yield functional channels, whereas no function is observed when the TW site and helix A, or the TW site and helix B are mutated simultaneously. Our data indicate that the TW site is dispensable for function, contributes to the stabilization of the CaM-Kv7.2 complex and becomes essential when docking to either helix A or when helix B is perturbed.