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

Hooley, Elizabeth; Papagrigoriou, Evangelos; Navdaev, Alexei; Pandey, Amit V; Clemetson, Jeannine M; Clemetson, Kenneth J; Emsley, Jonas (2008). The crystal structure of the platelet activator aggretin reveals a novel (alphabeta)2 dimeric structure. Biochemistry, 47(30), pp. 7831-7. Washington, D.C.: American Chemical Society 10.1021/bi800528t

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Clemetson, Jeannine and Clemetson, Kenneth John

ISSN:

0006-2960

ISBN:

18597489

Publisher:

American Chemical Society

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:05

Last Modified:

04 May 2014 23:20

Publisher DOI:

10.1021/bi800528t

PubMed ID:

18597489

Web of Science ID:

000257860100008

URI:

https://boris.unibe.ch/id/eprint/28205 (FactScience: 118564)

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