Fluorogenic Diversification of Unprotected Bromotryptophan by Aqueous Mizoroki-Heck Cross-Coupling

Gruß H, Belu C, Bernhard LM, Merschel A, Sewald N. Fluorogenic Diversification of Unprotected Bromotryptophan by Aqueous Mizoroki-Heck Cross-Coupling. Chemistry - A European Journal. 2019;25(23):5880-5883.Fluorescent styryl-tryptophans have been synthesized by a Mizoroki-Heck cross-coupling from unprotected bromotryptophan in aqueous medium showing promising spectrophotometric properties for possible application in fluorescence labelling of biomolecules. Moreover, this strategy permits a modular combination of biocatalytic halogenation by using immobilized FAD-dependent tryptophan halogenases and Pd-mediated chemocatalysis in a multistep one-pot process

HspB8 prevents aberrant phase transitions of FUS by chaperoning its folded RNA binding domain.

Aberrant liquid-to-solid phase transitions of biomolecular condensates have been linked to various neurodegenerative diseases. However, the underlying molecular interactions that drive aging remain enigmatic. Here, we develop quantitative time-resolved crosslinking mass spectrometry to monitor protein interactions and dynamics inside condensates formed by the protein fused in sarcoma (FUS). We identify misfolding of the RNA recognition motif (RRM) of FUS as a key driver of condensate ageing. We demonstrate that the small heat shock protein HspB8 partitions into FUS condensates via its intrinsically disordered domain and prevents condensate hardening via condensate-specific interactions that are mediated by its α-crystallin domain (αCD). These αCD-mediated interactions are altered in a disease-associated mutant of HspB8, which abrogates the ability of HspB8 to prevent condensate hardening. We propose that stabilizing aggregation-prone folded RNA-binding domains inside condensates by molecular chaperones may be a general mechanism to prevent aberrant phase transitions