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个人简介
My work is focused on understanding the molecular basis of signaling mechanisms mediated by G proteins, which are switch proteins. G proteins are normally inactive, but a receptor that has received a specific signal can activate G proteins, leading to changes in the activity of enzymes that produce second messengers such as cyclic AMP and calcium.
The resulting changes in cellular activity underlie a large number of physiological processes. G protein-mediated signalling cascades are key regulators of many physiological processes, including processes of development, differentiation, and regulation of cell division. In the brain, many key neurotransmitters and neuromodulators mediate a myriad of functions by activation of such G protein cascades.
The research in my laboratory is aimed at understanding how G proteins become activated by receptors, how they in turn activate effector enzymes, and how they turn off. We determined the sites of interaction between proteins using a method of decomposing the proteins into small synthetic peptides and determining which peptides blocked interaction sites (Hamm et al., 1988; Rarick et al., 1992; Artemyev et al., 1993; Arshavsky et al., 1994). To understand the process more fully, we determined the atomic structure of the proteins in collaboration with the group of Paul Sigler. We used X-ray crystallography to solve the three-dimensional structures of G proteins in their inactive (GDP bound, (Lambright et al., 1994) and activated (GTPbgS-bound) forms (Noel et al., 1993). We caught a glimpse of the self-inactivating process in another crystal form, the transition state analog, Ga.GDP.AlF4- (Sondek et al., 1994). More recently, the structures of the bg subunit (Sondek et al., 1996) and the heterotrimeric G protein (Lambright et al., 1996) were solved. These high-resolution structural studies allowed us to postulate specific hypotheses regarding mechanisms of receptor:G protein interaction and activation, G protein subunit association-dissociation and effector activation.
研究兴趣
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Shannon T. Smith, Jackson B. Cassada,Lukas Von Bredow,Kevin Erreger, Emma M. Webb, Trevor A. Trombley,Jacob J. Kalbfleisch,Brian J. Bender, Irene Zagol-Ikapitte,Valerie M. Kramlinger, Jacob L. Bouchard, Sidnee G. Mitchell,
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCEno. 4 (2024): 1086-1100
Neurobiology of aging (2024)
crossref(2023)
American journal of physiology Renal physiologyno. 2 (2023): F219-F226
Ryan P. Ceddia,Zack Zurawski,Analisa Thompson Gray,Feyisayo Adegboye, Ainsley McDonald-Boyer,Fubiao Shi,Dianxin Liu, Jose Maldonado, Jiesi Feng, Yulong Li, Simon Alford, Julio E. Ayala,
bioRxiv (Cold Spring Harbor Laboratory)pp.1-26, (2023)
Cell reportsno. 3 (2022): 110255-110255
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#Papers: 423
#Citation: 26767
H-Index: 74
G-Index: 158
Sociability: 7
Diversity: 3
Activity: 13
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