Biology subjects

Chattopadhyay, K.

Publications and source records attributed to Chattopadhyay, K..

24 records · Page 2Linked to original sources

bioRxiv2020

An exploration of the SARS-CoV-2 spike receptor binding domain (RBD), a complex palette of evolutionary and structural features

SARS-CoV-2 spike protein (S) is associated with the entry of virus inside the host cell by recruiting its loop dominant receptor binding domain (RBD) and interacting with the host ACE2 receptor. Our study deploying a two-tier approach encompassing evolutionary and structural analysis provides a comprehensive picture of the RBD, which could be of potential use for better understanding the RBD and address its druggability issues. Resorting to an ensemble of sequence space exploratory tools including co-evolutionary analysis and deep mutational scans we provide a quantitative insight into the evolutionarily constrained subspace of the RBD sequence space. Guided by structure network analysis and Monte Carlo simulation we highlight regions inside the RBD, which are critical for providing structural integrity and conformational flexibility of the binding cleft. We further deployed fuzzy C-means clustering by plugging the evolutionary and structural features of discrete structure blocks of RBD to understand which structure blocks share maximum overlap based on their evolutionary and structural features. Deploying this multi-tier interlinked approach, which essentially distilled the evolutionary and structural features of RBD, we highlight discrete region, which could be a potential druggable pocket thereby destabilizing the structure and addressing evolutionary routes.

biophysics↗

bioRxiv2020

Protein induced membrane phase transition facilitates leishmania infection

Although host membrane is known to play critical roles in the internalization of leishmania parasites inside macrophages (M{phi}), any detailed mechanistic understanding is missing. We show here that KMP-11, a small immunogenic protein of Leishmania Donovani (LD) facilitates the infection process by binding to M{phi} membrane through its N-terminal domain (1-19AA). This binding results in a membrane phase transition that occurs at a threshold protein/lipid ratio, which is linked to the change in membrane tension. KMP-11 induced phase transition is also associated with lipid raft disruption and T-cell deactivation. Finally, using a combination of tryptophan-scanning mutagenesis and synthesized peptides, we develop a mathematical exposition, which demonstrates that hydrophobic moment (H) and the number of residues involved in a mirror sequence (N) at the interacting N-terminal are governing factors for the membrane phase transition, which facilitates infection process.

biophysics↗

bioRxiv2020

Identification of QTLs for high grain yield and component traits in New Plant Types of rice

A panel of 60 genotypes consisting of New Plant Types (NPTs) along with indica, tropical and temperate japonica genotypes were phenotypically evaluated for four seasons in irrigated situation for grain yield per se and component traits. Twenty NPT genotypes were found to be promising with an average grain yield of 5.45 to 8.8 t/ha. A total of 85 SSR markers were used in the study to identify QTLs associated with grain yield per se and related traits. Sixty-six (77.65%) markers were found to be polymorphic. The PIC values varied from 0.516 to 0.92 with an average of 0.704. A moderate level of genetic diversity (0.39) was detected among genotypes. Variation to the tune of 8% within genotypes, 68% among the genotypes within the population and 24% among the populations were observed (AMOVA). The association analysis using GLM and MLM models led to the identification of 30 and 10 SSR markers were associated with 70 and 16 QTLs, respectively. Thirty novel QTLs linked with 16 SSRs were identified to be associated with eleven traits, namely, tiller number (qTL-6.1, qTL-11.1, qTL-4.1), panicle length (qPL-1.1, qPL-5.1, qPL-7.1, qPL-8.1), flag leaf length (qFLL-8.1, qFLL-9.1), flag leaf width (qFLW-6.2, qFLW-5.1, qFLW-8.1, qFLW-7.1), total no. of grains (qTG-2.2, qTG-a7.1), thousand-grain weight (qTGW-a1.1, qTGW-a9.2, qTGW-5.1, qTGW-8.1), fertile grains (qFG-7.1), seed length-breadth ratio (qSlb-3.1), plant height (qPHT-6.1, qPHT-9.1), days to 50% flowering (qFD-1.1) and grain yield per se (qYLD-5.1, qYLD-6.1a, qYLD-11.1). This information could be useful for identification of highly potential parents for development of transgressive segregants. Moreover, super rice genotypes could be developed through pyramiding of these QTLS for important yield traits for prospective increment in yield potentiality and breaking yield ceiling.

plant biology↗

bioRxiv2019

Heme minimizes Parkinson’s disease-associated toxicity by inducing a conformational distortion in the oligomers of alpha-Synuclein

Aggregation of the intrinsically disordered protein alpha-Synuclein (-Syn) into insoluble fibrils with a cross-{beta} sheet amyloid structure plays a key role in the neuronal pathology of Parkinsons disease (PD). The fibrillation pathway of -Syn encompasses a multitude of transient oligomeric forms differing in size, secondary structure, hydrophobic exposure and toxicity. According to a recent solid state NMR study, the fibrillating unit of -Syn contains the core residues of the protein arranged into in-register parallel {beta} sheets with a unique Greek key topology. Here, we have shown that the physiologically available small molecule heme (hemin chloride) when added at sub-stoichiometric ratios to either monomeric or aggregated -Syn, arrests its aggregation in an oligomeric state, which is minimally toxic. Using cryo-EM, we observed that these heme-induced oligomers are mace-shaped and consist of approximately four monomers. However, the presence of a crucial twist or contortion in their Greek key structural architecture prevents further hierarchical appending into annular oligomers and protofilament formation. We confirm using a His50Gln mutant that the binding of heme onto His50 is crucial in inflicting the structural distortion and is responsible for the stabilization of the non-toxic and off-pathway -Syn oligomers. We believe that this study provides a novel strategy of developing a therapeutic solution of PD, which has been elusive so far.

biophysics↗

bioRxiv2017

Electron microscopy reveals unique nano forms of bacterial spores

Endospore formation under environmental stress conditions is a well-established phenomenon for members of bacterial phylum Firmicutes, among which the most well studied ones belong to genus Bacillus and Clostridium. So far, known sizes of the spores are all larger than 500 nm. Nano-forms of bacteria have been reported but the notion still remains controversial. In this study, we provide visual evidences of living nano-entities (named here as nano-spores) formed by a bacterial species Bacillus cereus under prolonged stress, which are capable of escaping though standard sterile filtration procedure. The existence of nano-forms of bacteria was initially identified in a yeast ribosome preparation. We further demonstrate the transformation of the nano-spores into mature cells upon nutrient supply. Our study not only demonstrates the ability of bacteria to get transformed into yet-unknown form in order to survive under harsh environment, but also brings to light the existence of the smallest possible form of life.

microbiology↗

bioRxiv2017

Small Molecules Attenuate the Interplay between Conformational Fluctuations, Early Oligomerization and Amyloidosis of Alpha Synuclein

Aggregation of alpha synuclein has strong implications in Parkinsons disease. The heterogeneity of folding/aggregation landscape and transient nature of the early intermediates result in difficulty in developing a successful therapeutic intervention. Here we used fluorescence measurements at ensemble and single molecule resolution to study how the late and early events of alpha synuclein aggregation modulate each other. The in-vitro aggregation data was complemented using measurements inside live neuroblastoma cells by employing a small molecule labeling technique. An inhibitor molecule (arginine), which delayed the late event of amyloidosis, was found to bind to the protein, shifting the early conformational fluctuations towards a compact state. In contrast, a facilitator of late aggregation (glutamate), was found to be excluded from the protein surface. The presence of glutamate was found to speed up the oligomer formation at the early stage. We found that the effects of the inhibitor and facilitator were additive and as a result they maintained a ratio at which they cancelled each others influence on different stages of alpha synuclein aggregation.

biophysics↗