Bilobal architecture is a requirement for calmodulin signaling to Ca_V1.3 channels.

ABSTRACT: Calmodulin (CaM) regulation of voltage-gated calcium (Ca_V) channels is a powerful Ca²⁺ feedback mechanism that adjusts Ca²⁺ influx, affording rich mechanistic insights into Ca²⁺ decoding. CaM possesses a dual-lobed architecture, a salient feature of the myriad Ca²⁺-sensing proteins, where two homologous lobes that recognize similar targets hint at redundant signaling mechanisms. Here, by tethering CaM lobes, we demonstrate that bilobal architecture is obligatory for signaling to Ca_V channels. With one lobe bound, Ca_V carboxy tail rearranges itself, resulting in a preinhibited configuration precluded from Ca²⁺ feedback. Reconstitution of two lobes, even as separate molecules, relieves preinhibition and r

SUBMITTER: Banerjee R 

PROVIDER: S-EPMC5879666 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature