PDBsum entry 2r2i

Lyase activator

PDB id: 2r2i

Contents

Protein chain

184 a.a. *

Ligands

MYR

BME ×4

Metals

_CA ×3

Waters ×84

* Residue conservation analysis

PDB id:

2r2i

Name:

Lyase activator

Title:

Myristoylated guanylate cyclase activating protein-1 with calcium bound

Structure:

Guanylyl cyclase-activating protein 1. Chain: a. Fragment: guanylate cyclase activating protein-1. Synonym: gcap 1, guanylate cyclase activator 1a. Engineered: yes. Mutation: yes

Source:

Gallus gallus. Chicken. Organism_taxid: 9031. Gene: guca1a, gcap1. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.00Å R-factor: 0.218 R-free: 0.251

Authors:

R.Stephen

Key ref:

R.Stephen et al. (2007). Stabilizing function for myristoyl group revealed by the crystal structure of a neuronal calcium sensor, guanylate cyclase-activating protein 1. Structure, 15, 1392-1402. PubMed id: 17997965 DOI: 10.1016/j.str.2007.09.013

Date:

25-Aug-07 Release date: 11-Dec-07

Protein chain

P79880  (GUC1A_CHICK) -  Guanylyl cyclase-activating protein 1 from Gallus gallus

Seq: 199 a.a.

Struc: 184 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1016/j.str.2007.09.013

Structure 15:1392-1402 (2007)

PubMed id: 17997965

Stabilizing function for myristoyl group revealed by the crystal structure of a neuronal calcium sensor, guanylate cyclase-activating protein 1.

R.Stephen, G.Bereta, M.Golczak, K.Palczewski, M.C.Sousa.

ABSTRACT

Guanylate cyclase-activating proteins (GCAPs) are Ca(2+)-binding proteins myristoylated at the N terminus that regulate guanylate cyclases in photoreceptor cells and belong to the family of neuronal calcium sensors (NCS). Many NCS proteins display a recoverin-like "calcium-myristoyl switch" whereby the myristoyl group, buried inside the protein in the Ca(2+)-free state, becomes fully exposed upon Ca(2+) binding. Here we present a 2.0 A resolution crystal structure of myristoylated GCAP1 with Ca(2+) bound. The acyl group is buried inside Ca(2+)-bound GCAP1. This is in sharp contrast to Ca(2+)-bound recoverin, where the myristoyl group is solvent exposed. Furthermore, we provide direct evidence that the acyl group in GCAP1 remains buried in the Ca(2+)-free state and does not undergo switching. A pronounced kink in the C-terminal helix and the presence of the myristoyl group allow clustering of sequence elements crucial for GCAP1 activity.

Selected figure(s)

Figure 1.
Figure 1. Structure of MyrGCAP1 with Ca^2+ Bound
(A and B) Cartoon representation of myrGCAP1 in front (A) and back (B) views. The N-terminal helix is red, N-terminal domain (EF-1 and EF-2) is orange, C-terminal domain (EF-3 and EF-4) is yellow, kinked C-terminal helix is green, and the Ca^2+ ions and myristoyl group are shown as dark green and dark blue space-filling spheres, respectively.
(C and D) Surface representation of myrGCAP1 in front (C) and top (D) views. The surface is semitransparent to reveal the cartoon representation and the buried myristoyl group.

Figure 5.
Figure 5. Details Surrounding the Kink in the C-Terminal Helix of GCAP1
(A) The kink in the C-terminal helix and the side chains important for its stabilization are shown as sticks. The color scheme is as in Figure 1 and hydrogen bonds are shown as red dotted lines.
(B) Packing of Y98 (whose mutation to C98 is linked to retinal disease) among hydrophobic side chains (shown as sticks) between EF-3 and the kink of the C-terminal helix (in green sticks).

The above figures are reprinted from an Open Access publication published by Cell Press: Structure (2007, 15, 1392-1402) copyright 2007.

Figures were selected by an automated process.