2lsw

Publication Abstract from PubMed

Disabled-2 (Dab2) targets membranes and triggers a wide range of biological events, including endocytosis and platelet aggregation. Dab2, through its phosphotyrosine-binding (PTB) domain, inhibits platelet aggregation by competing with fibrinogen for alphaIIbbeta3 integrin receptor binding. We have recently shown that the N-terminal region, including the PTB domain (N-PTB), drives Dab2 to the platelet membrane surface by binding to sulfatides through two sulfatide-binding motifs, modulating the extent of platelet aggregation. The three-dimensional structure of a Dab2-derived peptide encompassing the sulfatide-binding motifs (SBM) has been determined in dodecylphosphocholine (DPC) micelles using NMR spectroscopy. Dab2 SBM contains two helices when embedded in micelles, reversibly binds to sulfatides with moderate affinity, lies parallel to the micelle surface, and, when added to a platelet mixture, reduces the number and size of sulfatide-induced aggregates. Overall, our findings identify and structurally characterize a minimal region in Dab2 that modulates platelet homotypic interactions, all of which provide the foundation for rational design of a new generation of anti-aggregatory low-molecular mass molecules for therapeutic purposes.

Structure, Sulfatide-binding Properties, and Inhibition of Platelet Aggregation by a Disabled-2-derived Peptide.,Xiao S, Charonko JJ, Fu X, Salmanzadeh A, Davalos RV, Vlachos PP, Finkielstein CV, Capelluto DG J Biol Chem. 2012 Sep 13. PMID:22977233^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.