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SUMMARY:Sequence-Based Determinants of  Aggregation within Protein Condens
 ates - Professor Monika Fuxreiter\, University of Padova
DTSTART:20240501T133000Z
DTEND:20240501T143000Z
UID:TALK210892@talks.cam.ac.uk
CONTACT:Lisa Masters
DESCRIPTION:Complex cellular landscapes of proteins include the dense\, li
 quid-like droplet state and the solid-like amyloid state\, in addition to 
 the native state. The amyloid state\, which is often pathological\, can be
  formed through the deposition pathway from the native state and through t
 he condensation pathway from the droplet state. I present a uniform framew
 ork to describe both pathways and identify mutations biasing towards these
  aggregation mechanisms. The droplet landscape model is a sequence-based\,
  generic approach that simultaneously estimates the probability of droplet
  formation and the likelihood of state conversion. The method exploits tha
 t the interactions driving the droplet state sample disordered binding mod
 es\, whereas those governing the amyloid state sample ordered binding mode
 s\, which can simultaneously be estimated from sequence without informatio
 n on the interaction partners. In addition\, we predict the multiplicity o
 f binding modes\, that a given protein region can sample under different c
 ellular conditions. I will demonstrate the application of the droplet land
 scape approach to both pathological and functional aggregates\, in particu
 lar predicting mutations associated with amyotrophic lateral sclerosis and
  those facilitating muscle lineage development. \n\n\nReferences\nM. Vendr
 uscolo\, M Fuxreiter (2022) Protein Condensation Diseases: Therapeutic Opp
 ortunities. Nat Commun 13\, 5500\, doi:  10.1038/s41467-022-32940-7\nHatos
  A\, Tosatto SCE\, Vendruscolo M\, Fuxreiter M. (2022) FuzDrop on AlphaFol
 d: visualizing the sequence-dependent propensity of liquid-liquid phase se
 paration and aggregation of proteins. Nucleic Acids Res. 50(W1)\, W337-44\
 nGönczi M.\, Teixeira JMC\, Barrera-Vilarmau  S.\, Mediani L. \, Antonian
 i F. \, Nagy TM\, Fehér K.\, Ráduly Z.\, Ambrus V.\, Tőzsér J.\, Barta
  E.\, Kövér KE.\, Csernoch L.\,  Carra S. \, Fuxreiter M. (2023) Alterna
 tively spliced exon regulates context-dependent MEF2D higher-order assembl
 y during myogenesis Nature Communications 14\, 1329.\nHorvath A\, Vendrusc
 olo M\, Fuxreiter M. (2022) Sequence-based Prediction of the Cellular Toxi
 city Associated with Amyloid Aggregation within Protein Condensates Bioche
 mistry 61\, 2461-2469.\n
LOCATION:Unilever Lecture Theatre\, Yusuf Hamied Department of Chemistry
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