All Disorder is Not Created Equal: Functional Disorder in Small Heat Shock Proteins
Molecular Horizons Seminar - Professor Rachel Klevit
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Wollongong Campus
28-101
A unifying mechanism by which the ATP-independent Small Heat Shock proteins (sHSP) delay aggregation of cellular proteins remains enigmatic. sHSPs share a conserved structured domain, the Alpha-Crystallin Domain, and high disorder content (>50%). The large, highly variable disordered region known as the N-terminal region (NTR) is required for chaperone activity and for oligomer assembly. Our holistic approaches that include hydrogen-deuterium exchange/mass spectrometry, UV-crosslinking/mass spectrometry, mass photometry, biochemical assays, and computational simulations have enabled us to identify key interactive regions in the NTRs of human sHSPs that are responsible for assembly and for chaperone activity. Results will be viewed through the lens of the previously proposed quasi-order model of sHSP structure and function.