FURTHER INSIGHT INTO THE STRUCTURAL AND REGULATORY PROPERTIES OF THE CGMP-GATED CHANNEL - AUTHORS RESPONSE

Recent studies from several different laboratories have provided furth er insight into structure-function relationships of cyclic nucleotide- gated channel and in particular the cGMP-gated channel of rod photorec eptors. Site-directed mutagenesis and rod-olfactory chimeria construct s have defined important amino acids and peptide segments of the chann el that are important in ion blockage, ligand specificity, and gating properties. Molecular cloning studies have indicated that cyclic nucle otide-gated channels consist of two subunits that we required to repro duce the properties of the native channels. Biochemical analysis of th e cGMP-gated channel of rodcells have indicated that the 240 kDa prote in that co-purifies with the 63 kDa channel subunit contains both the previously cloned second subunit of the channel and a glutamic acid-ri ch protein. The regulatory properties of the cGMP-gated channel from r od cells has also been studied in more detail. Studies indicate that t he beta subunit of the cGMP-gated channel of rod cells contains the bi nding site for calmodulin. Interaction of calmodulin with the channel alters the apparent affinity of the channel for cGMP in all in vitro s ystems that have been studied. The significance of these recent studie s are discussed in relation to the commentaries on the target article.