PDBsum entry 2vrp

Sugar binding protein

PDB id: 2vrp

Contents

Protein chains

133 a.a. *

123 a.a. *

Metals

_NA ×4

_CL ×2

Waters ×44

* Residue conservation analysis

PDB id:

2vrp

Name:

Sugar binding protein

Title:

Structure of rhodocytin

Structure:

Aggretin alpha chain. Chain: a. Synonym: rhodocytin. Aggretin beta chain. Chain: b. Fragment: residues 24-146. Synonym: rhodocytin

Source:

Calloselasma rhodostoma. Malayan pit viper. Organism_taxid: 8717. Organism_taxid: 8717

Resolution:

2.41Å R-factor: 0.204 R-free: 0.272

Authors:

A.A.Watson,C.A.O'Callaghan

Key ref:

A.A.Watson et al. (2008). Crystal structure of rhodocytin, a ligand for the platelet-activating receptor CLEC-2. Protein Sci, 17, 1611-1616. PubMed id: 18583525 DOI: 10.1110/ps.035568.108

Date:

09-Apr-08 Release date: 08-Jul-08

Protein chain

Q9I841  (SLYA_CALRH) -  Snaclec rhodocytin subunit alpha from Calloselasma rhodostoma

Seq: 136 a.a.

Struc: 133 a.a.

Protein chain

Q9I840  (SLYB_CALRH) -  Snaclec rhodocytin subunit beta from Calloselasma rhodostoma

Seq: 146 a.a.

Struc: 123 a.a.

DOI no: 10.1110/ps.035568.108

Protein Sci 17:1611-1616 (2008)

PubMed id: 18583525

Crystal structure of rhodocytin, a ligand for the platelet-activating receptor CLEC-2.

A.A.Watson, J.A.Eble, C.A.O'Callaghan.

ABSTRACT

Binding of the snake venom protein rhodocytin to CLEC-2, a receptor on the surface of human platelets, initiates a signaling cascade leading to platelet activation and aggregation. We have previously solved the structure of CLEC-2. The 2.4 A resolution crystal structure of rhodocytin presented here demonstrates that it is the first snake venom or other C-type lectin-like protein to assemble as a non-disulfide linked (alphabeta)(2) tetramer. Rhodocytin is highly adapted for interaction with CLEC-2 and displays a concave binding surface, which is highly complementary to the experimentally determined binding interface on CLEC-2. Using computational dynamic methods, surface electrostatic charge and hydrophobicity analyses, and protein-protein docking predictions, we propose that the (alphabeta)(2) rhodocytin tetramer induces clustering of CLEC-2 receptors on the platelet surface, which will trigger major signaling events resulting in platelet activation and aggregation.

Selected figure(s)

Figure 1.
Figure 1. Rhodocytin is an ( β)[2] tetrameric C-type lectin-like snake venom protein. (A) Rhodocytin forms a tetramer containing two copies of a disulfide linked β-heterodimer, whereas factor X-bp is dimeric, and convulxin is cyclic. - and β-chains are colored yellow and pink, respectively. Disulfide bonds in rhodocytin are colored green. (B) Each image represents the molecular surface of one rhodocytin β-heterodimer at the interface that forms the tetramer. In the upper panel, the hydrophobic surface is colored green. In the lower panel, negatively and positively charged regions are colored red and blue, respectively, from –7 to +7 kTe. (C) Hydrogen bonds are shown as broken blue lines between residues of the two -chains within the rhodocytin tetramer. For clarity, one -chain is colored yellow and the other red. For residues involved in hydrogen bonds, carbon atoms are colored light blue, oxygen is red, and nitrogen is dark blue.

The above figure is reprinted by permission from the Protein Society: Protein Sci (2008, 17, 1611-1616) copyright 2008.

Figure was selected by the author.

Author's comment

Rhodocytin is the first snake venom or other C-type lectin-like protein that has been shown to assemble as a non-disulfide linked (alpha-beta)₂ tetramer. Rhodocytin is highly adapted for interaction with CLEC-2 and displays a concave binding surface, which is highly complementary to the experimentally determined binding interface on CLEC-2. Using computational dynamic methods, surface electrostatic charge and hydrophobicity analyses, and protein-protein docking predictions, we propose that the (alpha-beta)₂ rhodocytin tetramer induces clustering of CLEC-2 receptors on the platelet surface, which will trigger major signaling events resulting in platelet activation and aggregation.