Intermolecular Interactions in the TMEM16A Dimer Controlling Channel Activity.

ABSTRACT: TMEM16A and TMEM16B are plasma membrane proteins with Ca²⁺-dependent Cl^- channel function. By replacing the carboxy-terminus of TMEM16A with the equivalent region of TMEM16B, we obtained channels with potentiation of channel activity. Progressive shortening of the chimeric region restricted the "activating domain" to a short sequence close to the last transmembrane domain and led to TMEM16A channels with high activity at very low intracellular Ca²⁺ concentrations. To elucidate the molecular mechanism underlying this effect, we carried out experiments based on double chimeras, Forster resonance energy transfer, and intermolecular cross-linking. We also modeled TMEM16A structure using the Nectria haematococca TMEM16 protein as template. Our results indicate t

SUBMITTER: Scudieri P 

PROVIDER: S-EPMC5144075 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature