| * Venue | E C G Sudarshan Hall |
| * Speaker | Milan Kumar Hazra |
| * Title | Stability and Dynamics in Biomolecular Condensates: A Molecular View |
| Affiliation | IIT Jodhpur |
| Abstract | Proteins with intrinsically disordered regions (IDRs) play a very crucial role in cellular phase separation, yet the diverse molecular forces that IDRs offer in driving phase separation are not yet fully understood. With an aim to elucidate how intrinsically disordered peptide sequences, particularly sequence charge pattern and the balance between peptides’ short- and long-range interactions with other peptides may affect the stability, structure and dynamics of protein condensates, we systematically explore the structural and dynamical features of condensates formed by a series of disordered polyampholytes that differ either in terms of their charged amino acid distribution along the sequence or in terms of the ratio of short-range dispersion interactions to long-range electrostatics interactions. Increased charge clustering raises the critical temperature for phase separation and results in each polyampholyte experiencing a larger number of inter-chain contacts with neighboring proteins in the condensate. Consequently, polyampholytes with greater charge clustering adopt a much more extended conformation than that observed in dilute bulk phase. The liquid-like environment in the condensate is reflected in the polymers’ high conformational entropy (which is higher than that in the bulk) and pronounced translational diffusion in the dense phase being only 4-20 times slower than dilute bulk phase. As the fraction of mutations that participate in short-range interactions increases at the expense of long-range electrostatic interactions, a significant decrease in the critical temperature of phase separation is observed. Decreased condensate stability is coupled with decreased translational diffusion of the polymers in the condensate, which may result in the loss of liquid characteristics in the presence of a high fraction of uncharged residues. To investigate the thermodynamic basis of recently observed ultra-high affinity in extremely charged binary fuzzy protein complexes, a microscopic replica of multibody biomolecular condensates, we have observed an entropy-enthalpy reinforcement dictates a dramatic increase in binding affinity while sequence characteristics vary from polyampholytes toward polyelectrolytes. In our latest study, blending structure-based bottom-up coarse-graining approach and bioinformatic analysis, we have unraveled a dual nature of proline residues that modulates the conformational ensemble in naturally occurring IDRs depending on their spatial organization within protein sequence. This finding is significant as prolines are the most common residue type in IDRs. |
| * Announcement? | Institute |
| * Refreshments? | After the event |
| * Honorarium? | Faculty |
| Special Arrangements? | None |
| * Host name and email | Debayan Chakraborty @@ debayan@imsc.res.in |