As part of the series Life Science & Chemistry Department Seminar
Prof. Janine Kirstein, Professor of Cell Biology, University of Bremen
will give a talk entitled:
Remodelling of amyloid proteins by dynamic chaperone complexes
Huntington disease is caused by a polyglutamine expansion in the first exon of the huntingtin gene (HTTEx1). The resulting mutant protein of HTTEx1 is known to aggregate into insoluble inclusion bodies. A trimeric chaperone complex composed of Hsc70, DNAJB1 and Apg2 suppresses the fibrilization of HttEx1 and also resolubilises Htt aggregates. We could identify a 9 aa sequence within the C-terminal domain of DNAJB1 as binding site for the interaction with HttEx1. DNAJB1 as well as Hsc70 bind to the polyproline region of HttEx1 just adjacent to the glutamines. And while the increased number of glutamines positively correlates with aggregation propensity and onset of HD, the impact of the domains flanking this stretch is not well studied or understood. To bridge this gap, we generated C. elegans strains expressing human HTTEx1 and variations that either lack the polyproline domain or exhibit an expanded proline stretch. Employing fluorescent lifetime imaging (FLIM) we identify the polyproline domain as a strong protector against aggregation that could have evolved in humans to buffer the aggregation of an expanded polyglutamine stretch.
All are kindly welcome!
Further information by the host of the guest speaker:
Prof. Dr. Klaudia Brix, Professor of Cell Biology - Email: k.brix [at] jacobs-university.de - Tel: +49 421 200-3246 /- Link to Homepage: http://www.jacobs-university.de/ses/kbrix