Crystal Structure of Rhodocytin, a Ligand for the Platelet-activating Receptor CLEC-2

Overview

Journal Protein Sci

Specialty Biochemistry

Date 2008 Jun 28

PMID 18583525

Citations 20

Authors

Aleksandra A Watson

Johannes A Eble

Chris A OCallaghan

Affiliations

Soon will be listed here.

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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