2VRP

Crystal Structure of Rhodocytin, a Ligand for the Platelet-Activating Receptor Clec-2.

(2008) Protein Sci 17: 1611

• PubMed: 18583525 Search on PubMedSearch on PubMed Central
• DOI: https://doi.org/10.1110/ps.035568.108
• Primary Citation of Related Structures:  
  2VRP


• PubMed Abstract: 
  

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

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Organizational Affiliation: 

Henry Wellcome Building for Molecular Physiology, University of Oxford, Oxford OX3 7BN, United Kingdom.