The molecular mechanism of Hsp90-induced oligomerization of Tau

• DOI: 10.1101/614289
• Publication Date: 2019-04-20T00:06:11Z
• Authors: Sabrina Weickert; Magdalena Wawrzyniuk; Laura John; Stefan G. D. Rüdiger; Malte Drescher
• Keywords: Tau protein; Chaperone (clinical)

Abstract Aggregation of the microtubule-associated protein Tau is a hallmark Alzheimer’s disease with oligomers suspected as most toxic agent. client Hsp90, though it unclear whether and how chaperone massages structure intrinsically disordered Tau. Using electron paramagnetic resonance, we extract structural information from very broad conformational ensemble Tau: in solution highly dynamic polymorphic, ‘paper-clip’-shaped by long-range contacts. Interaction Hsp90 promotes an open conformation, which identify molecular basis for formation small exposure aggregation-prone repeat domain to other molecules. At same time, fibrils inhibited. We therefore provide nanometer-scale zoom into chaperoning amyloid client, highlighting consequence this biologically relevant interaction.