Structure, sulfatide binding properties, and inhibition of platelet aggregation by a disabled-2 protein-derived peptide. Xiao, S., Charonko, J. J., Fu, X., Salmanzadeh, A., Davalos, R. V., Vlachos, P. P., Finkielstein, C. V., & Capelluto, D. G. J Biol Chem, 287(45):37691-702, 2012. 1083-351x Xiao, Shuyan Charonko, John J Fu, Xiangping Salmanzadeh, Alireza Davalos, Rafael V Vlachos, Pavlos P Finkielstein, Carla V Capelluto, Daniel G S Journal Article Research Support, Non-U.S. Gov't United States 2012/09/15 J Biol Chem. 2012 Nov 2;287(45):37691-702. doi: 10.1074/jbc.M112.385609. Epub 2012 Sep 13.doi abstract bibtex 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 α(IIb)β(3) 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 has been determined in dodecylphosphocholine micelles using NMR spectroscopy. Dab2 sulfatide-binding motif 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.
@article{RN208,
author = {Xiao, S. and Charonko, J. J. and Fu, X. and Salmanzadeh, A. and Davalos, R. V. and Vlachos, P. P. and Finkielstein, C. V. and Capelluto, D. G.},
title = {Structure, sulfatide binding properties, and inhibition of platelet aggregation by a disabled-2 protein-derived peptide},
journal = {J Biol Chem},
volume = {287},
number = {45},
pages = {37691-702},
note = {1083-351x
Xiao, Shuyan
Charonko, John J
Fu, Xiangping
Salmanzadeh, Alireza
Davalos, Rafael V
Vlachos, Pavlos P
Finkielstein, Carla V
Capelluto, Daniel G S
Journal Article
Research Support, Non-U.S. Gov't
United States
2012/09/15
J Biol Chem. 2012 Nov 2;287(45):37691-702. doi: 10.1074/jbc.M112.385609. Epub 2012 Sep 13.},
abstract = {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 α(IIb)β(3) 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 has been determined in dodecylphosphocholine micelles using NMR spectroscopy. Dab2 sulfatide-binding motif 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.},
keywords = {Adaptor Proteins, Signal Transducing/*chemistry/genetics/metabolism
Amino Acid Motifs
Amino Acid Sequence
Apoptosis Regulatory Proteins
Binding Sites
Circular Dichroism
Humans
Micelles
Models, Molecular
Molecular Sequence Data
Peptides/*chemistry/metabolism/*pharmacology
Phosphorylcholine/analogs & derivatives/chemistry
Platelet Adhesiveness/drug effects
Platelet Aggregation/*drug effects
Protein Binding
Protein Structure, Secondary
Protein Structure, Tertiary
Sequence Homology, Amino Acid
Sulfoglycosphingolipids/*chemistry/metabolism
Surface Plasmon Resonance
Tumor Suppressor Proteins/*chemistry/genetics/metabolism},
ISSN = {0021-9258 (Print)
0021-9258},
DOI = {10.1074/jbc.M112.385609},
year = {2012},
type = {Journal Article}
}
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J. and Fu, X. and Salmanzadeh, A. and Davalos, R. V. and Vlachos, P. P. and Finkielstein, C. V. and Capelluto, D. G.},\n title = {Structure, sulfatide binding properties, and inhibition of platelet aggregation by a disabled-2 protein-derived peptide},\n journal = {J Biol Chem},\n volume = {287},\n number = {45},\n pages = {37691-702},\n note = {1083-351x\nXiao, Shuyan\nCharonko, John J\nFu, Xiangping\nSalmanzadeh, Alireza\nDavalos, Rafael V\nVlachos, Pavlos P\nFinkielstein, Carla V\nCapelluto, Daniel G S\nJournal Article\nResearch Support, Non-U.S. Gov't\nUnited States\n2012/09/15\nJ Biol Chem. 2012 Nov 2;287(45):37691-702. doi: 10.1074/jbc.M112.385609. Epub 2012 Sep 13.},\n abstract = {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 α(IIb)β(3) integrin receptor binding. 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