PDBsum entry 3bx4

Toxin

PDB id: 3bx4

Contents

Protein chains

132 a.a. *

122 a.a. *

Ligands

SO4 ×9

GOL

Waters ×324

* Residue conservation analysis

PDB id:

3bx4

Name:

Toxin

Title:

Crystal structure of the snake venom toxin aggretin

Structure:

Aggretin alpha chain. Chain: a, c. Aggretin beta chain. Chain: b, d

Source:

Agkistrodon rhodostoma. Malayan pit viper. Secretion: venom. Secretion: venom

Resolution:

1.70Å R-factor: 0.204 R-free: 0.236

Authors:

E.Hooley,E.Papagrigoriou,A.Navdaev,A.Pandey,J.M.Clemetson, K.J.Clemetson,J.Emsley

Key ref:

E.Hooley et al. (2008). The crystal structure of the platelet activator aggretin reveals a novel (alphabeta)2 dimeric structure. Biochemistry, 47, 7831-7837. PubMed id: 18597489

Date:

11-Jan-08 Release date: 26-Aug-08

Protein chains

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

Seq: 136 a.a.

Struc: 132 a.a.

Protein chains

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

Seq: 146 a.a.

Struc: 122 a.a.

Biochemistry 47:7831-7837 (2008)

PubMed id: 18597489

The crystal structure of the platelet activator aggretin reveals a novel (alphabeta)2 dimeric structure.

E.Hooley, E.Papagrigoriou, A.Navdaev, A.V.Pandey, J.M.Clemetson, K.J.Clemetson, J.Emsley.

ABSTRACT

Aggretin is a C-type lectin purified from Calloselasma rhodostoma snake venom. It is a potent activator of platelets, resulting in a collagen-like response by binding and clustering platelet receptor CLEC-2. We present here the crystal structure of aggretin at 1.7 A which reveals a unique tetrameric quaternary structure. The two alphabeta heterodimers are arranged through 2-fold rotational symmetry, resulting in an antiparallel side-by-side arrangement. Aggretin thus presents two ligand binding sites on one surface and can therefore cluster ligands in a manner reminiscent of convulxin and flavocetin. To examine the molecular basis of the interaction with CLEC-2, we used a molecular modeling approach of docking the aggretin alphabeta structure with the CLEC-2 N-terminal domain (CLEC-2N). This model positions the CLEC-2N structure face down in the "saddle"-shaped binding site which lies between the aggretin alpha and beta lectin-like domains. A 2-fold rotation of this complex to generate the aggretin tetramer reveals dimer contacts for CLEC-2N which bring the N- and C-termini into the proximity of each other, and a series of contacts involving two interlocking beta-strands close to the N-terminus are described. A comparison with homologous lectin-like domains from the immunoreceptor family reveals a similar but not identical dimerization mode, suggesting this structure may represent the clustered form of CLEC-2 capable of signaling across the platelet membrane.