3BX4

Crystal structure of the snake venom toxin aggretin

Summary for 3BX4

• Entry DOI: 10.2210/pdb3bx4/pdb
• Descriptor: Aggretin alpha chain, Aggretin beta chain, SULFATE ION, ... (5 entities in total)
• Functional Keywords: toxin
• Biological source: Agkistrodon rhodostoma (Malayan pit viper); More
• Cellular location: Secreted: Q9I841 Q9I840
• Total number of polymer chains: 4
• Total formula weight: 66161.60

Authors

Hooley, E.,Papagrigoriou, E.,Navdaev, A.,Pandey, A.,Clemetson, J.M.,Clemetson, K.J.,Emsley, J. (deposition date: 2008-01-11, release date: 2008-08-26, Last modification date: 2024-10-30)

Primary citation

Hooley, E.,Papagrigoriou, E.,Navdaev, A.,Pandey, A.V.,Clemetson, J.M.,Clemetson, K.J.,Emsley, J.
The crystal structure of the platelet activator aggretin reveals a novel (alphabeta)2 dimeric structure.
Biochemistry, 47:7831-7837, 2008

PubMed 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.

PubMed: 18597489
DOI: 10.1021/bi800528t

Experimental method

X-RAY DIFFRACTION (1.7 Å)