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Seminar in Biochemistry, Biophysics & Biodesign: Ioannis Gelis, Univ. of South Florida

Speaker: Ioannis Gelis,  Assistant Professor Department of Chemistry, Univ. of South Florida Tampa, FL

Title: Molecular insights into the progression of Hsp90-mediated kinase chaperone cycle

Abstract: Molecular chaperones play an essential role in the maintenance of a balanced protein homeostasis, by promoting protein folding and preventing protein misfolding and aggregation. Broad scope chaperones such as those found in the heat shock protein (Hsp) family, including Hsp60, Hsp70, Hsp90, Hsp100 and small Hsps, do not function independently but make the core of elaborate macromolecular machineries formed with partner proteins, termed cochaperones, that regulate their functions, fine-tune progression through the chaperone cycle and even bridge chaperone machineries, creating intricate chaperone networks. Thus, the composition and architecture of chaperone complexes is highly dynamic, requiring remodeling of protein-protein interfaces for efficient processing of the substrate during chaperone cycles. We use NMR spectroscopy together with other biophysical and biochemical techniques to characterize early steps of the Hsp90-mediated chaperone cycle of protein kinases, and particularly substrate entry. I will discuss how the kinase-specific cochaperone of Hsp90, Cdc37, assists in the recruitment of protein kinases and essentially orchestrates progression through the kinase chaperone cycle. Sensing of kinase thermodynamic stability permits Cdc37 to discriminate between client- and non-client kinases and therefore allows for selective client entry to the chaperone cycle. Phosphorylation induced unfolding of Cdc37, coupled to global conformational rearrangements, then lead to the release of the cochaperone and possessing of the substrate kinase assisted by a series of late cochaperones implicated in regulating the ATPase activity of Hsp90.

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Event Information

February 19
12:00 pm - 1:00 pm
ASRC Auditorium
85 St. Nicholas Terrace
New York, NY 10031 United States
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