NMR Structures of Calmodulin Bound to Two Separate Regulatory Sites in the Retinal Cyclic Nucleotide-Gated Channel.

ABSTRACT: Retinal cyclic nucleotide-gated (CNG) channels (composed of three CNGA1 and one CNGB1 subunits) exhibit a Ca²⁺-induced reduction in channel open probability mediated by calmodulin (CaM). Defects in the Ca²⁺-dependent regulation of CNG channels may be linked to autosomal recessive retinitis pigmentosa and other inherited forms of blindness. Here, we report the NMR structure and binding analysis of CaM bound to two separate sites within CNGB1 (CaM1: residues 565-589 and CaM2: residues 1120-1147). Our binding studies reveal that CaM1 binds to the Ca²⁺-bound CaM N-lobe with at least fivefold higher affinity than it binds to the CaM C-lobe. By contrast, the CaM2 site binds to the Ca²⁺-bound CaM C-lobe with higher affinity than it binds to the N-lobe.

SUBMITTER: Bej A 

PROVIDER: S-EPMC9810080 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature