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Protein Structure Report

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

¹ University of Oxford;
² University of Frankfurt

(RECEIVED April 10, 2008; ACCEPTED June 16, 2008)

Binding of the snake venom protein rhodocytin to CLEC-2, a receptor on the surface of human platelets, initiates a signalling cascade leading to platelet activation and aggregation. We have previously solved the structure of CLEC-2. The 2.4Angstrom 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 (β)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 (β)2 rhodocytin tetramer induces clustering of CLEC-2 receptors on the platelet surface, which will trigger major signalling events resulting in platelet activation and aggregation.

Keywords: Structure; Crystallography; Protein crystallization; Computational Analysis of Protein Structure; Molecular mechanics/dynamics; Docking Proteins; Protein Structures - New

³ E-mail: chris.ocallaghan{at}ndm.ox.ac.uk

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