Peter Tompa1,2
1VIB-VUB Center for Structural Biology, Brussels, Belgium
2Vrije Universiteit Brussel (VUB), Dept. DBIT, Brussels, Belgium
peter.tompa [at] vub.be
Abstract
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.
Keywords: LLPS databases, LLPS mechanism, LLPS targeting, condensatopathy, ALS/FTD
