Accepted for publication (PostPrint)
ROS-GC1 membrane guanylate cyclase is a Ca(2+) bimodal signal transduction switch. It is turned "off" by a rise in free Ca(2+) from nanomolar to the semicromolar range in the photoreceptor outer segments and the olfactory bulb neurons; by a similar rise in the bipolar and ganglion retinal neurons it is turned "on". These opposite operational modes of the switch are specified by its Ca(2+) sensing devices, respectively termed GCAPs and CD-GCAPs. Neurocalcin delta is a CD-GCAP. In the present study, the neurocalcin delta-modulated site, V(837)-L(858), in ROS-GC1 has been mapped. The location and properties of this site are unique. It resides within the core domain of the catalytic module and does not require the alpha-helical dimerization domain structural element (amino acids 767-811) for activating the catalytic module. Contrary to the current beliefs, the catalytic module is intrinsically active; it is directly regulated by the neurocalcin delta-modulated Ca(2+) signal and is dimeric in nature. A fold recognition based model of the catalytic domain of ROS-GC1 was built, and neurocalcin delta docking simulations were carried out to define the three-dimensional features of the interacting domains of the two molecules. These findings define a new transduction model for the Ca(2+) signaling of ROS-GC1.
Venkataraman, Venkateswar; Duda, Teresa; Ravichandran, Sarangan; and Sharma, Rameshwar, "Neurocalcin δ Modulation of ROS-GC1, a New Model of Ca2+ Signaling†" (2008). School of Osteopathic Medicine Faculty Scholarship. 30.
Venkataraman V, Duda T, Ravichandran S, Sharma RK. Neurocalcin delta modulation of ROS-GC1, a new model of Ca(2+) signaling. Biochemistry. 2008 Jun 24;47(25):6590-601. doi: 10.1021/bi800394s. PMID: 18500817. PMCID: PMC2844899.