PDBsum entry 2ggz

Lyase activator

PDB id: 2ggz

Contents

Protein chain

165 a.a. *

Metals

_CA ×6

* Residue conservation analysis

PDB id:

2ggz

Name:

Lyase activator

Title:

Crystal structure of human guanylate cyclase activating protein-3

Structure:

Guanylyl cyclase-activating protein 3. Chain: a, b. Synonym: gcap 3, guanylate cyclase activator 1c. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.

Resolution:

3.00Å R-factor: 0.256 R-free: 0.290

Authors:

R.Stephen

Key ref:

R.Stephen et al. (2006). The crystal structure of GCAP3 suggests molecular mechanism of GCAP-linked cone dystrophies. J Mol Biol, 359, 266-275. PubMed id: 16626734 DOI: 10.1016/j.jmb.2006.03.042

Date:

24-Mar-06 Release date: 23-May-06

Protein chains

O95843  (GUC1C_HUMAN) -  Guanylyl cyclase-activating protein 3 from Homo sapiens

Seq: 209 a.a.

Struc: 165 a.a.

DOI no: 10.1016/j.jmb.2006.03.042

J Mol Biol 359:266-275 (2006)

PubMed id: 16626734

The crystal structure of GCAP3 suggests molecular mechanism of GCAP-linked cone dystrophies.

R.Stephen, K.Palczewski, M.C.Sousa.

ABSTRACT

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.

Selected figure(s)

Figure 1.
Figure 1. Crystal structure of GCAP3. (a) Ribbon diagram of GCAP3. The segments of polypeptide containing the four EF-hands are colored as follows: EF-hand 1 is deep blue (aa 21-47), EF-hand 2 is light blue (aa 48-87), EF-hand 3 is red (aa 88-125), EF-hand 4 is orange (aa 126-161); the C-terminal helix is colored green (aa 162-185). (b) Superposition of GCAP3 and calmodulin based on EF-hands 3 and 4. The color scheme is the same as for (a), with the N-terminal domain of calmodulin colored grey. All Figures were prepared using Pymol (http://www.pymol.org).

Figure 3.
Figure 3. Surface residue conservation in GCAPs. Residues conserved among GCAPs and GCIP (see the text) were mapped onto the surface of GCAP3. Strictly conserved residues that do not participate in Ca^2+ coordination (non-EF-hand) are colored deep blue. Highly conserved residues are colored medium blue. Conserved EF-hand residues are colored cyan. (a) Side view with the N-terminal domain up and the C terminus down (a cartoon representation of GCAP3 colored as for Figure 1 is shown). (b) Side view rotated 180° with respect to (a). (c) Top view rotated 90° with respect to (a) shows the N-terminal domain of GCAP3. (d) Bottom view, rotated 180° with respect to (c) showing the C-terminal domain.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2006, 359, 266-275) copyright 2006.

Figures were selected by an automated process.