Description of Research Expertise:
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.
Litvinov, R.I., Mravic, M., Zhu, H., Weisel, J.W., DeGrado, W.F., and Bennett, J.S.: Unique transmembrane domain interactions differentially modulate integrin avb3 and aIIbb3 function. Proc. Natl. Acad. Sci. U.S.A. 116 : 11195-12300,2019.
Tan, S.K., Fong, K.P., Polizzi, N.F., Sternisha, A., Slusky, J.S.G., Yoon, K., DeGrado, W.F., and Bennett, J.S.: Modulating integrin aIIbb3 activity through mutagenesis of allosterically regulated inter-subunit contacts Biochemistry 58 : 3251-3259,2019.
Mravic, M., Hu, H., Lu, Z., Bennett, J.S., Sanders, C.R., Orr, A.W., and DeGrado, W.F.: De novo designed transmembrane peptides activating the 51 integrin. Protein: De novo designed transmembrane peptides activating the 51 integrin. Protein Engineering, Design & Selection. : 2018.
Kononova, O., Litvinov, R.I., Blokhin, D.S., Klochkov, V.V., Weisel, J.W., Bennett, J.S., Barsegov, V.: Mechanistic basis for the binding of RGD- and AGDV-peptides to the platelet integrin IIb3. Biochemistery 56 : 2017.
Bennett, J.S.: Are anti-platelet agents beneficial in Essential Thrombocythemia? Maybe yes, probably no. Ann. Int. Med. 167 : 206-207,2017.
Bennett, J.S.: Clinical dilemma: Experts make the call. ASH Clinical News. 3 (05): 34,2017.
Bennett, J.S.: IIb3 (GPIIb/IIIa) structure and function Platelets in Thrombotic and Non-Thrombotic Disorders 2 : 99-109,2017.
Höök, P., Litvinov, R.I., Kim, O.V., Xu, S., Bennett, J.S., Alber, M.S., and Weisel, J.W: Strong binding of platelet integrin IIb3 to fibrin clots: Potential target to destabilize thrombi. Scientific Reports 7 : 2017.
Huntington, S.F., O’Hara, M.O., and Bennett, J.S: Platelet disorders: clinical and laboratory evaluation. Non-Malignant Hematology: Expert Clinical Perspective : 171-184,2016.
Fong, F.P., Zhu, H., Span, L.M., Moore, D.T., Yoon, K., Tamura, R., Yin, H.H., DeGrado, W.F., and Bennett, J.S.: Directly activating IIb3 initiates outside-in signaling by causing IIb3 clustering J. Bio. Chem/ 291 : 2016.
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