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914 BRB II/III/6160 |
Integrin function
is essential for normal platelet adhesion and aggregation and participates
i n the formation of the arterial thrombi that are responsible for heart
attacks and strokes. The activation state of platelet integrins
is regulated by platelet agonists, but the structural basis for this regulation
is not known. Our studies indicate that helix-helix interactions
involving the transmembrane and membrane-proximal cytoplasmic domain segments
play an essential role in regulating the function of both beta 1 and beta
3 integrins. The current focus of the laboratory is to use biophysical
and molecular biologic techniques to characterize these interactions in
detail and to use this information to design potential anti-thrombotic
agents. Selected Publications: Litvinov, R.I., G. Vilaire, H. Shuman, J.S. Bennett, and J.W. Weisel Quantitative analysis of platelet avb3 binding to osteopontin using laser tweezers. J. Biol. Chem. (in press) Li, R., N. Mitra, H. Gratkowski, G. Vilaire, R.I. Litvinov, C. Nagaswami, J.W. Weisel, J.D. Lear, W.F. DeGrado, and J.S. Bennett (2003) Activation of integrin aIIbb3 by modulation of transmembrane helix associations. Science 300:795-798. Li, R., R.H. Hoess, J.S. Bennett,
and W.F. DeGrado (2003) Use of phage display to probe the evolution of
binding specificity and affinity in integrins. Protein Engineering
16: 65-72. Li, R., C.R. Babu, K. Valentine, J.D. Lear, A.J. Wand, J.S. Bennett, and W.F. DeGrado (2002) Characterization of the monomeric form of the transmembrane and cytoplasmic domains of the integrin b3 subunit by NMR spectroscopy. Biochemistry 41:15618-15624. Litvinov, R.I., H. Shuman, J.S. Bennett, and J.W. Weisel (2002) Intermolecular forces between fibrinogen-integrin pairs measured by laser tweezers. Proc. Natl. Acad. Sci. USA 99: 7426-7431. Li, R., C.R. Babu, J.D. Lear, A.J. Wand, J.S. Bennett, and W.F. DeGrado (2001) Oligomerization of the integrin aIIbb3: Roles of the transmembrane and cytoplasmic domains. Proc. Natl. Acad. Sci. USA 98:12462-12467. |
