The Crystal Structure of the Platelet Activator Aggretin Reveals a Novel (αβ)2 Dimeric Structure
| Autor: | Kenneth J. Clemetson, Alexei Navdaev, Evangelos Papagrigoriou, Jeannine M. Clemetson, Amit V. Pandey, Elizabeth Hooley, Jonas Emsley |
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| Rok vydání: | 2008 |
| Předmět: |
Membrane Glycoproteins
Molecular model Chemistry Stereochemistry Dimer Convulxin Viper Venoms Crystal structure Crystallography X-Ray Biochemistry Protein Structure Secondary Protein Structure Tertiary chemistry.chemical_compound Tetramer Docking (molecular) Mutation Animals Humans Lectins C-Type Protein quaternary structure Binding site Dimerization Protein Binding |
| Zdroj: | Biochemistry. 47:7831-7837 |
| ISSN: | 1520-4995 0006-2960 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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