Biotechnology and Biosciences Seminar - giovedì 23 febbraio, 2023, ore 15:00, edificio BIOS, aula U3-08 / Webex
Salvador Ventura, IBB, Universitat Autònoma de Barcelona, Spain
Architecture of a toxic alpha-synuclein oligomer
a-synuclein oligomers (aSO) are key drivers of neurodegeneration in Parkinson's disease (PD). However, their structure remains elusive. We have determined the architecture of aSO, dissecting the properties of individual chains within these toxic assemblies. We demonstrate that the NAC domain does not suffice to promote oligomer to fibril conversion; instead, this transition is controlled by a short N-terminal motif. A missense mutation causing early-onset PD remodels this region, which results in long-lived aSO that elude the human Hsp70 machinery. Our results provide structural understanding of oligomer to amyloid conversion and identify targets for therapeutic intervention
Peter Tompa (1, 2) 1. VIB, VIB-VUB Center for Structural Biology, Brussels, Belgium. 2. Vrije Universiteit Brussel (VUB), Dept. DBIT, Brussels, Belgium
Targeting liquid-liquid phase separation in disease: a new modality in drug development?
Biomolecular condensation is a process whereby many macromolecules (proteins and RNAs) form non-stoichiometric, functional assemblies. The dominant mechanism of such biomolecular condensation is liquid-liquid phase separation (LLPS), which leads to the formation of membraneless organelles (MLOs), such as the nucleolus and stress granules, in the cell. The proteins involved often have a high proportion of intrinsic structural disorder, which drive LLPS by transient, multivalent interactions. As MLOs play key roles in cell signaling, the misregulation of their formation and dissolution often leads to diseases termed “condensatopathies”. In my presentation, I will outline the basic mechanisms leading to such disease states, focusing on cancer, viral infections and neurodegeneration. I will also discuss the different potential strategies for correcting these errors in cell signaling, and show through specific examples how drug candidates, “c-mods” capable of correcting MLO misregulation, can be developed.
LINK per partecipare al seminario: https://unimib.webex.com/unimib-it/j.php?MTID=me8221b43fa571a09b839b63cf15b69e6
password: day23 (32923 da telefoni)
Il seminario è APERTO a tutti.
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