Signal Transduction
Functional Study and Mapping Sites for Interaction with the Target Enzyme in Retinal Degeneration 3 (RD3) Protein
Retinal degeneration 3 (RD3) protein, essential for normal expression of retinal membrane guanylyl cyclase (RetGC) in photoreceptor cells, blocks RetGC catalytic activity and stimulation by guanylyl cyclase-activating proteins (GCAPs). In a mouse retina, RD3 inhibited both RetGC1 and RetGC2 isozymes. Photoreceptors in the rd3/rd3 mouse retinas lacking functional RD3 degenerated more severely than in the retinas lacking both RetGC isozymes, consistent with a hypothesis that the inhibitory activity of RD3 has a functional role in photoreceptors.Dimerization Domain of Retinal Membrane Guanylyl Cyclase 1 (RetGC1) Is an Essential Part of Guanylyl Cyclase-activating Protein (GCAP) Binding Interface
Background: GCAPs regulate photoreceptor guanylyl cyclase RetGC1 but not hormone receptor guanylyl cyclase NPRA.Results: Mutations in RetGC1 dimerization domain disrupt GCAP1 and GCAP2 binding.Conclusion: Met823 in dimerization domain strongly contributes to its specificity in forming GCAP binding interface.Significance: Congenital blindness-causing mutation in the neighboring residue prohibits GCAP binding.
