2ggz
From Proteopedia
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Crystal Structure of Human Guanylate Cyclase Activating Protein-3
Overview
Absorption of light by visual pigments initiates the phototransduction, pathway that results in degradation of the intracellular pool of, cyclic-GMP (cGMP). This hydrolysis promotes the closing of cGMP-gated, cation channels and consequent hyperpolarization of rod and cone, photoreceptor cell membranes. Guanylate cyclase-activating proteins, (GCAPs) are a family of proteins that regulate retinal guanylate cyclase, (GC) activity in a Ca2+-dependent manner. At high [Ca2+], typical of the, dark-adapted state (approximately 500 nM), GCAPs inhibit retinal GCs. At, the low [Ca2+] (approximately 50 nM) that occurs after the closing of, cGMP-gated channels, GCAPs activate retinal GCs to replenish dark-state, cGMP levels. Here, we report the crystal structure of unmyristoylated, human GCAP3 with Ca2+ bound. GCAP3 is an EF-hand Ca2+-binding protein with, Ca2+ bound to EF2, 3 and 4, while Ca2+ binding to EF-hand 1 is disabled., GCAP3 contains two domains with the EF-hand motifs arranged in a tandem, array similar to GCAP2 and members of the recoverin subfamily of, Ca2+-binding proteins. Residues not involved in Ca2+ binding, but, conserved in all GCAPs, cluster around EF1 in the N-terminal domain and, may represent the interface with GCs. Five point mutations in the closely, related GCAP1 have been linked to the etiology of cone dystrophies. These, residues are conserved in GCAP3 and the structure suggests important roles, for these amino acids. We present a homology model of GCAP1 based on GCAP3, that offers insight into the molecular mechanism underlying the autosomal, dominant cone dystrophies produced by GCAP1 mutations.
About this Structure
2GGZ is a Single protein structure of sequence from Homo sapiens with CA as ligand. Full crystallographic information is available from OCA.
Reference
The crystal structure of GCAP3 suggests molecular mechanism of GCAP-linked cone dystrophies., Stephen R, Palczewski K, Sousa MC, J Mol Biol. 2006 Jun 2;359(2):266-75. Epub 2006 Apr 3. PMID:16626734
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