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Pause-conférence | Pr Ansgar Siemer (USA)
23 janvier 2020 @ 12:00 - 13:00 EST
La surface des fibrilles de l’exon-1 huntingtin: effets sur les interactions et la toxicité des protéines
Le Pr Ansgar Siemer, professeur à la University of Southern California, sera l’invité de la Pre Isabelle Marcotte le Jeudi 23 janvier 2020 à 12h00 au PK-1140.
En savoir plus sur les recherches du Pr Siemer (anglais).
The surface of huntingtin exon-1 fibrils: effects on protein interactions and toxicity
Pr Ansgar Siemer, a professor at University of Southern California, will be the guest of Pre Isabelle Marcotte on Thursday January 23rd at 12:00 in PK-1140
Learn more about Pr Siemer’s research.
Summary: A mechanism of potential cross-β (amyloid) fibril toxicity in neurodegenerative diseases will have to be mediated by the (abnormal) interaction of the fibril with cellular binding partners. We are studying the fibril surface in the context of huntingtin exon-1 (HTTex1) important in Huntington’s Disease (HD). HD is a debilitating neurodegenerative disease caused by mutant huntingtin with an expanded polyQ region containing more than 35 consecutive Gln residues. The core of HTTex1 fibrils is formed by the expanded polyQ domain. The Pro-rich C-terminus of HTTex1 fibrils is highly dynamic as shown by solid-state NMR and EPR. Consequently, we proposed a bottle brush model of HTTex1 fibrils in which the C-terminus forms the surface of the fibrils in the form of dynamic bristles. We show that the differences between HTTex1 fibrils of different toxicity are located in the C-terminus rather then the polyQ domain. Small fibrils with highly dynamic C-termini are more seeding competent, more accessible to protein-protein interaction, and more toxic than long, entangled fibrils.
The C-terminus of HTTex1 is an intrinsically disordered protein domain i.e. is has no well defined structure but changes conformation rapidly over time. Therefore, we used solid-state NMR and EPR in combination with MD simulations to describe the dynamics and conformational space the HTTex1 C-terminus. With a detailed description of the HTTex1 fibril surface in hand, we are now studying the interaction of HTTex1 C-terminus with chaperons that can disaggregate HTTex1 fibrils.
Un évènement organisé dans le cadre des Pause-conférences du CERMO-FC et soutenu par :
An event organized as part of the Pause-conférences of CERMO-FC, and support by :
