Biology subjects

Biswas, P.

Publications and source records attributed to Biswas, P..

41 records · Page 3Linked to original sources

bioRxiv2019

Gliotoxin, identified from a screen of fungal metabolites, disrupts 7SK snRNP, releases P-TEFb and reverses HIV-1 latency

A leading pharmacological strategy towards HIV cure requires "shock" or activation of HIV gene expression in latently infected cells with Latency Reversal Agents (LRAs) followed by their subsequent clearance. In a screen for novel LRAs we used fungal secondary metabolites (extrolites) as a source of bio-active molecules. Using orthogonal mass spectrometry (MS) coupled to latency reversal bioassays, we identified gliotoxin (GTX) as a novel LRA. GTX significantly induced HIV-1 gene expression in latent ex vivo infected primary cells and in CD4+ T cells from all aviremic HIV-1+ participants. RNA sequencing identified 7SK RNA, the scaffold of the P-TEFb inhibitory 7SK snRNP complex to be significantly reduced upon GTX treatment of independent donor CD4+T cells. GTX disrupted 7SK snRNP, releasing active P-TEFb, which then phosphorylated RNA Pol II CTD, inducing HIV transcription. Our data highlight the power of combining a medium throughput bioassay, mycology and orthogonal mass spectrometry to identify novel potentially therapeutic compounds.

molecular biology↗

bioRxiv2019

The viral SUMO-targeted Ubiquitin Ligase ICP0 is phosphorylated and activated by host kinase Chk2

When the Herpes Simplex virus (HSV) genome enters the nucleus for replication and transcription, phase-segregated nuclear protein bodies called PML Nuclear Bodies (PML NBs) colocalize with the genome and repress it. HSV encodes a SUMO-targeted Ubiquitin ligase ICP0 that degrades PML NBs to alleviate the repression. The molecular mechanism used by ICP0 to target PML NBs is unclear. For reasons unknown, the growth of HSV is dependent on the ATM/Chk2 pathway. Here we identify a bonafide SUMO-Interacting motif in ICP0 (SLS4) that is essential and sufficient to target SUMOylated proteins in PML NBs like PML and Sp100. Phosphorylation of SLS4 creates new salt-bridges between SUMO and SLS4, increases the SUMO/SLS4 affinity and switches ICP0 into a potent STUbL. We also report that ICP0 exploits the kinase Chk2 to phosphorylate SLS4 and enhance its STUbL activity. Our results uncover how a viral STUbL counters antiviral response by exploiting an unprecedented mechanism involving three post-translational modifications; ubiquitination, SUMOylation, and phosphorylation.

biochemistry↗

bioRxiv2019

Larval growth and survival in Indian Butter Catfish, Ompok bimaculatus (Bloch): effect of light intensity and photoperiod

Two sequential indoor rearing trials each of 21 days duration were conducted to investigate the effect of light intensity and photoperiod respectively on the growth and survival of Ompok bimaculatus larvae. In first trial, five different light intensities viz. 0, 300, 500, 900, 1200 lx were applied randomly to 800 larvae (0.003 g; 0.51 cm) stocked in triplicate following a completely randomized design into aquarium (30.0 x 15.0 x 15.0 cm) tanks. Sequentially, in second trial, five photoperiod cycles (light: dark, L: D) namely, 24L: 0D, 16L: 8D, 12L: 12D, 8L: 16D and 0L: 24D in combination with the best performing light intensity (300 lx) as observed from the first trial were employed in triplicates in similar set up. From the first trial, significantly higher survival was observed in 0 and 300 lx, whereas growth was highest in 900 lx (P < 0.05). In the second trial, survival was higher in continuous darkness (0L: 24D), whereas, maximum growth was recorded in 24L: 0D and 16L: 8D groups (P < 0.05). Performance index (PI) showed no significant difference (P > 0.05) among 0 and 300 lx light intensities, but were reduced at higher light intensities. The lowest PI was found in 12L: 12D and 8L: 16D condition but did not have any effect in other photoperiod cycles. Overall, from the present study it can be concluded that growth of the larvae is found to be higher in higher light intensity (900lx) and longer photoperiodic cycles (24L: 0D and 16L: 8D), however, better survival was recorded in total dark conditions suggesting that continuous dark condition is recommended for better hatchery performance of the larvae.

animal behavior and cognition↗

bioRxiv2017

Salt-bridge Dynamics in Intrinsically Disordered Proteins: A trade-off between electrostatic interactions and structural flexibility

Intrinsically Disordered Proteins (IDPs) are enriched in charged and polar residues; and, therefore, electrostatic interactions play a predominant role in their dynamics. In order to remain multi-functional and exhibit their characteristic binding promiscuity, they need to retain considerable dynamic flexibility. At the same time, they also need to accommodate a large number of oppositely charged residues, which eventually lead to the formation of salt-bridges, imparting local rigidity. The formation of salt-bridges therefore oppose the desired dynamic flexibility. Hence, there appears to be a meticulous trade-off between the two mechanisms which the current study attempts to unravel. With this objective, we identify and analyze salt-bridges, both as isolated as well as composite ionic bond motifs, in the molecular dynamic trajectories of a set of appropriately chosen IDPs. Time evolved structural properties of these salt-bridges like persistence, associated secondary structural 'order-disorder' transitions, correlated atomic movements, contribution in the overall electrostatic balance of the proteins have been studied in necessary detail. The results suggest that the key to maintain such a trade-off over time is the continuous formation and dissolution of salt-bridges with a wide range of persistence. Also, the continuous dynamic interchange of charged-atom-pairs (coming from a variety of oppositely charged side-chains) in the transient ionic bonds supports a model of dynamic flexibility concomitant with the well characterized stochastic conformational switching in these proteins. The results and conclusions should facilitate the future design of salt-bridges as a mean to further explore the disordered-globular interface in proteins.

bioinformatics↗

bioRxiv2017

Nitric oxide sensing by chlorophyll a

Nitric oxide (NO) acts as a signalling molecule that has direct and indirect regulatory roles in various functional processes in biology, though in plant kingdom its role is relatively unexplored. One reason for this is the fact that sensing of NO is always challenging. There are very few probes that can classify the different NO species. The present paper proposes a simple but straightforward way for sensing different NO species using chlorophyll, the source of inspiration being hemoglobin that serves as a NO sink in most mamalian system. The proposed method is able to classify NO from DETA-NONOate or (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl) amino] diazen-1-ium-1,2-diolate, nitrite, nitrate and S-nitrosothiol or SNO. This discrimination is carried out by chlorophyll a (chl a) at nano molar (nM) order of sensitivity and at 293K to 310K. Molecular docking reveals the differential binding behaviour of NO and SNO with chlorophyll, the predicted binding affinity matching with the experimental observation. Additional expreiments with diverse range of cyanobacteria reveals that apart from spectroscopic approach the proposed sensing module can be used in microscopic inspection of NO speices. Binding of NO is sensitive to tempertaure and static magnetic field. This provides additional support to the involvement of the porphyrin ring structure to the NO sensing process. This also broadens the scope of the sensing methods as hinted in the text.

bioengineering↗