Vijay Rangachari

Seminar Details

Host: Dr. Dzmitry Kurouski

Time: 4:00 pm- 5:00 pm

Location: BICH 108

Seminar Abstract

Biomolecular condensates (BCs) are membraneless hubs enriched with proteins and nucleic acids that have emerged as important players in many cellular functions. Uncovering the sequence determinants of proteins for phase separation is essential in understanding the biophysical and biochemical properties of BCs. Despite significant discoveries in the past decade, the role of cysteine residues in BC formation and dissolution has remained unknown. There is an enigmatic relationship between Cysteines and protein disorder, and we have shown that they can play a distinct role in aggregation and phase separation. Recently, to uncover the involvement of disulfide cross-links and their redox sensitivity in BCs, we designed a “stickers and spacers” model of phase-separating peptides interspersed with cysteines. Through biophysical investigations, we discovered that cysteines facilitate liquid−liquid phase separation under oxidizing conditions and stabilize liquid condensates through disulfide cross-links, which can be reversibly tuned using redox chemistry. By varying the composition of cysteines, subtle but distinct changes in the viscoelastic behavior of the condensates were observed. Empirically, we conclude that cysteines function neither as stickers nor spacers but as covalent nodes to lower the effective concentrations for sticker interactions and inhibit system-spanning percolation networks. Together, we unmask the possible role of cysteines in the formation of biomolecular condensates and their potential use as tunable covalent cross-linkers in developing redox-sensitive viscoelastic materials

Biomolecular Condensates.