Biology subjects

Biswas, S.

Publications and source records attributed to Biswas, S..

At least 91 records · Page 5Linked to original sources

bioRxiv2023

Helicity of a tardigrade disordered protein promotes desiccation tolerance

In order to survive extreme drying (anhydrobiosis), many organisms, spanning every kingdom of life, accumulate intrinsically disordered proteins (IDPs). For decades, the ability of anhydrobiosis-related IDPs to form transient amphipathic helices has been suggested to be important for promoting desiccation tolerance. However, evidence empirically supporting the necessity and/or sufficiency of helicity in mediating anhydrobiosis is lacking. Here we demonstrate that the linker region of CAHS D, a desiccation-related IDP from tardigrades that contains significant helical structure, is the protective portion of this protein. Perturbing the sequence composition and grammar of the linker region of CAHS D, through the insertion of helix-breaking prolines, modulating the identity of charged residues, sequence scrambling, or replacement of hydrophobic amino acids with serine or glycine residues results in variants with different degrees of helical structure. Importantly, the resulting helicity of these variants generated through similar helix breaking modalities correlates strongly with their ability to promote desiccation tolerance, providing direct evidence that helical structure is necessary for robust protection conferred by this desiccation-related IDP. However, correlation of protective capacity and helical content in variants generated through different helix perturbing modalities do not show as strong a trend, suggesting that while helicity is important it is not the only property that makes a protein protective during desiccation. These results provide direct evidence for the decades old theory that helicity of desiccation-related IDPs is linked to their anhydrobiotic capacity.

biochemistry↗

bioRxiv2023

Labile assembly of a tardigrade protein induces biostasis

Tardigrades are microscopic animals that survive desiccation by inducing biostasis. To survive drying tardigrades rely on intrinsically disordered CAHS proteins that form gels. However, the sequence features and mechanisms underlying gel formation and the necessity of gelation for protection have not been demonstrated. Here we report a mechanism of gelation for CAHS D similar to that of intermediate filaments. We show that gelation restricts molecular motion, immobilizing and protecting labile material from the harmful effects of drying. In vivo, we observe that CAHS D forms fiber-like condensates during osmotic stress. Condensation of CAHS D improves survival of osmotically shocked cells through at least two mechanisms: reduction of cell volume change and reduction of metabolic activity. Importantly, condensation of CAHS D is reversible and metabolic rates return to control levels after CAHS condensates are resolved. This work provides insights into how tardigrades induce biostasis through the self-assembly of CAHS gels.

physiology↗

bioRxiv2023

In silico characterization of five novel disease-resistance proteins in Oryza sativa sp. japonica against bacterial leaf blight and rice blast diseases

Oryza sativa sp. japonica is the most widely cultivated variety of rice. It has evolved several defense mechanisms, including PAMP-triggered immunity (PTI) and effector-triggered immunity (ETI), which provide resistance against different pathogens to overcome biotic stresses. Several disease-resistance genes and proteins, such as R genes and PRR proteins, have been reported in the scientific literature which shows resistance against Xanthomonas oryzae pv. oryzae (Xoo), a causative agent for bacterial leaf blight disease (BB), and Magnaporthe oryzae (M. oryzae), causing rice blast disease (RB). Although some of these resistance proteins have been studied, the functional characterization of resistance proteins in rice is not exhaustive. In the current study, we identified five novel resistance proteins against BB and RB diseases through gene network analysis. Structure and function prediction, disease-resistance domain identification, protein-protein interaction (PPI), and pathway analysis revealed that the five new proteins played a role in the disease resistance against BB and RB. In silico modeling, refinement, and model quality assessment were performed to predict the best structures of these five proteins, and submitted to ModelArchive for future use. The functional annotation of the proteins revealed their involvement in the bacterial disease resistance of rice. We predicted that the new resistance proteins could be localized to the nucleus and plasma membrane. This study provides insight into developing disease-resistant rice varieties by predicting novel candidate resistance proteins, which will pave the way for their future characterization and assist rice breeders in improving crop yield and addressing future food security.

bioinformatics↗

bioRxiv2023

Host inducible-HSP70A1A is an irresistible drug target to combat SARS-CoV-2 infection and pathogenesis

One of the fundamental mechanisms developed by the host to contain the highly infectious and rapidly proliferating SARS coronavirus is elevation of body temperature, a natural fallout of which is Heat Shock Protein (HSP) over-expression. Here, for the first time, we demonstrate that the SARS-CoV-2 virus exploits the host Hsp70 chaperone for its entry and propagation and blocking it can combat the infection. SARS-CoV-2 infection as well as febrile temperature enhanced Hsp70 overexpression in host Vero E6 cells. In turn, Hsp70 overexpression elevated the host cell autophagic response that is a prerequisite for viral propagation. Suppressive and prophylactic treatment of Vero E6 cells with HSP70 inhibitor PES-Cl, a small molecule derivative of Pifithrin , abrogated viral infection more potently than the currently used drug Remdesivir by suppressing host HSP70 and autophagic response. In conclusion, our study not only provides a fundamental insight into the role of host Hsp70 in SARS-CoV-2 pathogenesis, it paves the way for the development of potent and irresistible anti-viral therapeutics.

microbiology↗

bioRxiv2023

An in-silico approach to study the molecular interaction of the PINK1 kinase domain with Parkin Ubl domain

Parkinsons Disease (PD) is the second most common neurodegenerative disorder which creates devastating effects on the neurons of the mid brain. PARK2 and PARK6 genes encode the E3 ubiquitin ligase Parkin and serine/threonine protein kinase PINK1 (PTEN-induced kinase 1), respectively. Mutations in these proteins are responsible for majority of the early onset of PD. PINK1 protein along with Parkin are known to participate in the mitochondrial mitophagy pathway which selectively removes damaged mitochondria. Parkin with the help of its intra-domain interactions goes to an autoinhibited inactive state. Parkin ubiquitin activity is suppressed in this condition. Phosphorylation of the Serine65 residue, present in the Ubl domain of Parkin, is required for its ubiquitin ligase activity. PINK1 protein phosphorylates the Serine65 residue after its self-phosphorylation. After activation, Parkin protein ubiquitinates other damaged mitochondrial proteins for their degradation. Therefore, PINK1-Parkin interaction is important for the proper maintenance of the mitochondrial and neuronal fidelity. In this present work, we are trying to find out how the mutations in the PINK1 kinase domain would affect the modes of its interaction with the Ubl domain of Parkin. We used the three dimensional coordinates of the PINK1 and Ubl domain of Parkin from our previous work and selected the mutations P296L and G309D which have the abilities to hamper the said interactions between PINK1 and the Ubl domain of Parkin. We used molecular docking followed by molecular dynamics simulations to study the nature and structural dynamics of the binding interactions. The results from our study could provide an insight into the PINK1 mediated Parkin activation and plausible biochemical mechanism behind the onset of PD.

bioinformatics↗

bioRxiv2023

Molecular insight into the mechanism of action of some beneficial flavonoids for the treatment of Parkinson's Disease

Parkinsons Disease (PD) is a severe neurodegenerative disorder. It is characterized by the declination of dopaminergic (DA) neurons of substantia nigra pars compacta in the mid brain. Decrease in dopamine level in substantia nigra is a major event in PD. Mutation in Parkin protein is responsible for the onset of Autosomal Recessive Juvenile Parkinsons (ARJP) Disease. Till date, there is no available treatment of PD without any side-effects. Therefore, the focus has been shifted to identifying natural product inhibitors for the treatment of the disorder. Flavonoids, a class of natural products, have proven neuroprotective effects. Some of the flavonoids have their abilities to influence the activities of central nervous system. Therefore, many studies are being conducted to analyze their activities to lower the progression of neurodegenerative diseases. This study was conducted to identify the flavonoids to be used as potential drugs for PD. From the literature, we picked up the flavonoids active on the nervous systems of human beings. We employed a literature mining approach to build a Structure Activity Relationship (SAR) to measure their efficacies. We performed molecular docking simulations using the flavonoids as the ligands and computed their binding free energy values. Our study would therefore point towards future drug- designing endeavours to come up with plausible therapeutics against PD onset.

bioinformatics↗

bioRxiv2023

H3K9 methylation enhances HP1-associated epigenetic silencing complex assembly and suppresses off-chromatin binding

Visualizing and measuring molecular-scale interactions in living cells represents a major challenge, but recent advances in microscopy are bringing us closer to achieving this goal. Single-molecule super-resolution microscopy enables high-resolution and sensitive imaging of the positions and movement of molecules in living cells. HP1 proteins are important regulators of gene expression because they selectively bind and recognize H3K9 methylated (H3K9me) histones to form heterochromatin-associated protein complexes that silence gene expression. Here, we extended live-cell single-molecule tracking studies in fission yeast to determine how HP1 proteins interact with their binding partners in the nucleus. We measured how genetic perturbations that affect H3K9me alter the diffusive properties of HP1 proteins and each of their binding partners based on which we inferred their most likely interaction sites. Our results indicate that H3K9me promotes specific complex formation between HP1 proteins and their interactors in a spatially restricted manner, while attenuating their ability to form off-chromatin complexes. As opposed to being an inert platform or scaffold to direct HP1 binding, our studies propose a novel function for H3K9me as an active participant in enhancing HP1-associated complex formation in living cells.

biophysics↗

bioRxiv2023

Comprehensive codon usage analyses of the mutations in the Parkin protein leading to Parkinsonism

Neurodegenerative diseases typically occur due to the abnormal behavior of the proteins. One of the most prevalent neurodegenerative diseases is the Parkinsons disease. Parkin protein encoded by PARK2 gene is the central player in the central nervous system. Mutations in Parkin lead to the onset of Parkinsonism. In this work, we made an attempt to decipher the codon usage patterns of the amino acid residues in the different domains of Parkin protein. We observed that mutations at the first two codon positions have statistically significant disease associations. This is the first such report that analyzes the correlation between the disease severity of Parkinsonism and its association with the pattern of codon usages.

bioinformatics↗

bioRxiv2022

A duration-dependent interaction between high-intensity light and optical refocus in the drive for myopia control

PURPOSETo evaluate the duration-dependent and synergetic impact of high-intensity light (HL) and optical refocus (RF) on lens-induced myopia (LIM) development in chickens. METHODSMyopia was induced in one eye in chicks (10 groups, n=126) from day 1 post- hatching (D1) until D8 using -10D lenses. Fellow eyes remained uncovered as controls. Nine groups were exposed daily to continuous 2 hours (h), 4h, or 6h of either HL (15,000 lux); RF (removal of -10D lens); or both (HL+RF). One group served as the LIM group without any interventions. Ocular axial length (AL), refractive error, and choroidal thickness were measured on D1, D4, and D8. Outcome measures are expressed as inter-ocular difference (IOD= experimental - control eye) {+/-}SEM. RESULTSBy D8, LIM increased AL (0.36{+/-}0.04 mm), myopic refraction (-9.02{+/-}0.37D), and choroidal thinning (-90.27{+/-}16.44 {micro}m) in the LIM group (all, P<0.001). Compared to the LIM group, exposure to 2h, 4h, or 6h of HL, RF, or HL+RF reduced myopic refraction in a duration-dependent manner, with RF being more effective than HL (P<0.05). Only 6h of HL+RF (not 2h or 4h) prevented LIM and was more effective than RF (P=0.004) or HL (P<0.001) in reducing myopic refraction, and more effective than HL (P<0.001) in reducing axial elongation. CONCLUSIONDaily exposure to 2h, 4h, or 6h of HL, RF, or HL+RF reduced lens-induced myopic refraction in a duration-dependent manner in chickens. Only 6h of HL+RF completely stopped LIM development. The synergetic effect of HL and RF is dependent on the duration of the interventions.

neuroscience↗

bioRxiv2022

Structural characterizations of a unusual peptide CORO1C-47aa encoded by circRNA hsa-circ-0000437 associated with endometrial cancer

Circular RNAs, which have covalently closed ends, is a special type of non-coding RNAs. Recent studies reveal that they are associated with various biochemical pathways. One such involvements of circular RNAs is in the onset of different types of cancers. Though the circular RNAs are known as non-coding RNAs, however, some of them are found to possess the capacities to code for proteins. One such circular RNA is hsa-circ-0000437 which is known to code for a short peptide referred to as CORO1C-47aa. The peptide has anti-angiogenic activity and are associated with the prevention of endometrial cancer. However, till date only the amino acid sequence of the peptide is known and no structural details of the peptide are available. Therefore, in this work, our aim was to predict how the peptide would fold and what could be its possible ligand binding sites. We used computational tools to determine the structure of the peptide. The structure was refined by molecular dynamics simulations. The possible binding sites and the binding partners of the peptide were also predicted. From this structure function analysis study, we tried to elucidate the possible mechanism of the involvements of the peptide in the onset of endometrial cancer. This is the first report on the structural characterization of the peptide. This study may therefore be useful in determining the structures of new drug candidates for the treatment of endometrial cancer.

bioinformatics↗

bioRxiv2022

Natural and engineered mediators of desiccation tolerance stabilize Human Blood Clotting Factor VIII in a dry state

Biologics, pharmaceuticals containing or derived from living organisms, such as vaccines, antibodies, stem cells, blood, and blood products are a cornerstone of modern medicine. However, nearly all biologics have a major deficiency: they are inherently unstable, requiring storage under constant cold conditions. The so-called cold-chain, while effective, represents a serious economic and logistical hurdle for deploying biologics in remote, underdeveloped, or austere settings where access to cold-chain infrastructure ranging from refrigerators and freezers to stable electricity is limited. To address this issue, we explore the possibility of using anhydrobiosis, the ability of organisms such as tardigrades to enter a reversible state of suspended animation brought on by extreme drying, as a jumping off point in the development of dry storage technology that would allow biologics to be kept in a desiccated state under ambient or even elevated temperatures. Here we examine the ability of different protein and sugar-based mediators of anhydrobiosis derived from tardigrades and other anhydrobiotic organisms to stabilize Human Blood Clotting Factor VIII under repeated dehydration/rehydration cycles, thermal stress, and long-term dry storage conditions. We find that while both protein and sugarbased protectants can stabilize the biologic pharmaceutical Human Blood Clotting Factor FVIII under all these conditions, protein-based mediators offer more accessible avenues for engineering and thus tuning of protective function. Using classic protein engineering approaches, we fine tune the biophysical properties of a protein-based mediator of anhydrobiosis derived from a tardigrade, CAHS D. Modulating the ability of CAHS D to form hydrogels made the protein better or worse at providing protection to Human Blood Clotting Factor VIII under different conditions. This study demonstrates the effectiveness of tardigrade CAHS proteins and other mediators of desiccation tolerance at preserving the function of a biologic without the need for the cold-chain. In addition, our study demonstrates that engineering approaches can tune natural products to serve specific protective functions, such as coping with desiccation cycling versus thermal stress. Ultimately, these findings provide a proof of principle that our reliance on the cold-chain to stabilize life-saving pharmaceuticals can be broken using natural and engineered mediators of desiccation tolerance.

pharmacology and toxicology↗

bioRxiv2022

Single-cell RNA sequencing implicates venous endothelial cells as a source of VEGF-mediated neo-angiogenesis in neuroinflammation

Histopathological studies of multiple sclerosis (MS), a demyelinating disease of the central nervous system (CNS), and its animal model, experimental autoimmune encephalomyelitis (EAE), have found newly formed leaky vessels in demyelinated acute and chronic plaques, in addition to blood-brain barrier (BBB) damage in existing vessels, that exacerbate disease pathology by increasing infiltration of immune cells. Which vessel subtypes and signaling pathways generate these aberrant vessels is poorly understood. Using single-cell RNA-sequencing and in vivo validation, we find that transcriptome signatures of neo-angiogenesis arise in venous endothelial cells in both acute and chronic EAE, and correlate with upregulation in VEGF-A signaling. These neo-angiogenic markers are also increased in acute and chronic MS lesions. Treatment with a VEGF-A blocking antibody diminishes neo-angiogenic transcriptomic signatures and vascular proliferation in vivo, but does not restore BBB function or ameliorate significantly EAE pathology. Therefore, anti-angiogenic therapies in combination with immunomodulatory therapies may benefit MS progression.

neuroscience↗

bioRxiv2022

Cd-induced cytosolic proteome changes in the cyanobacterium Anabaena sp. PCC7120 are mediated by LexA as one of the regulatory proteins

LexA, a well-characterized transcriptional repressor of the SOS genes in heterotrophic bacteria, has been shown to regulate diverse genes in cyanobacteria. An earlier study showed that LexA overexpression in a cyanobacterium, Anabaena sp. PCC7120 reduces its tolerance to Cd stress. This was later shown to be due to modulation of photosynthetic redox poising by LexA under Cd stress. However, in light of the global regulatory nature of LexA and the prior prediction of AnLexA-box in a few heavy metal-responsive genes, we speculated that LexA has a broad role in Cd stress tolerance, with regulation over a variety of Cd stress-responsive genes in addition to the regulation on genes related with photosynthetic redox poising. Thus, to further expand the knowledge on the regulatory role of LexA in Cd stress tolerance, a cytosolic proteome profiling of Anabaena constitutively overexpressing LexA upon Cd stress was performed. The proteomic study revealed 25 differentially accumulated proteins (DAPs) in response to the combined effect of LexA overexpression and Cd stress, and the other 11 DAPs exclusively in response to either LexA overexpression or Cd stress. The 36 identified proteins were related with a variety of functions, including photosynthesis, carbon metabolism, antioxidative defence, protein turnover, chaperones, post-transcriptional modifications, and a few unknown and hypothetical proteins. The regulation of LexA on corresponding genes, as well as six previously reported Cd efflux transporters, was further validated by the presence of AnLexA-boxes, transcript, and/or promoter analyses. In a nutshell, this study identifies the regulation of LexA on several genes and proteins of various functional categories in Anabaena that are responsive to Cd stress, hence expanding the regulatory role of LexA under Cd stress. HighlightsO_LILexA overexpression was earlier shown to decrease Cd stress tolerance in Anabaena. C_LIO_LIWe examined the combined effect of LexA overexpression and Cd on Anabaena proteome. C_LIO_LIUpon LexA overexpression or Cd stress or both, 36 differential proteins were found. C_LIO_LIIn silico, transcript and EMSA proved LexA regulation on them and few transporters. C_LIO_LIThe findings of this study extended the regulatory role of LexA in Cd tolerance. C_LI

molecular biology↗

bioRxiv2022

Chaperonin activity of Plasmodium prefoldin complex is essential to guard proteotoxic stress response and presents a new target for drug discovery

The intraerythrocytic growth of malaria parasite is challenged by the presence of proteotoxic stress and intrinsically unstructured proteins in the cytoplasm due to formation of toxic heme during haemoglobin digestion. To overcome the unavoidable stress and maintain the cellular protein homeostasis, parasite encodes for a number of chaperones and co-chaperones. Here, we functionally characterize the Plasmodium falciparum prefoldins (PfPFD1-6), a hexameric co-chaperone complex, for their role in protein homeostasis. We demonstrate that PfPFD1-6 localise to cytosol of the parasite and the subunits perform an orchestrated interaction (-PFD3-PFD2-PFD1-PFD5-PFD6-PFD4-) to form an active jelly-fish like complex. Biperiden, an N-propylpiperidine analogue identified by chemotype search from FDA, strongly binds and restricts the formation of prefoldin complex and inhibited its interaction with the substrates, PfMSP-1 and -tubulin-I. Biperiden treatment potently inhibited the in vitro (IC50: 1M) and in vivo growth of malaria parasite. Thus, this study provides novel virtues towards understanding the role of PfPFDs in regulating protein homeostasis and opens new avenues for drug discovery against malaria.

molecular biology↗

bioRxiv2022

Molecular engineering of a cryptic epitope in Spike RBD improves manufacturability and neutralizing breadth against SARS-CoV-2 variants

There is a continued need for sarbecovirus vaccines that can be manufactured and distributed in low- and middle-income countries (LMICs). Subunit protein vaccines are manufactured at large scales at low costs, have less stringent temperature requirements for distribution in LMICs, and several candidates have shown protection against SARS-CoV-2. We previously reported an engineered variant of the SARS-CoV-2 Spike protein receptor binding domain antigen (RBD-L452K-F490W; RBD-J) with enhanced manufacturability and immunogenicity compared to the ancestral RBD. Here, we report a second-generation engineered RBD antigen (RBD-J6) with two additional mutations to a hydrophobic cryptic epitope in the RBD core, S383D and L518D, that further improved expression titers and biophysical stability. RBD-J6 retained binding affinity to human convalescent sera and to all tested neutralizing antibodies except antibodies that target the class IV epitope on the RBD core. K18-hACE2 transgenic mice immunized with three doses of a Beta variant of RBD-J6 displayed on a virus-like particle (VLP) generated neutralizing antibodies (nAb) to nine SARS-CoV-2 variants of concern at similar levels as two doses of Comirnaty. The vaccinated mice were also protected from challenge with Alpha or Beta SARS-CoV-2. This engineered antigen could be useful for modular RBD-based subunit vaccines to enhance manufacturability and global access, or for further development of variant-specific or broadly acting booster vaccines.

bioengineering↗

bioRxiv2022

The cost of sympatry: spatio-temporal patterns in leopard dietary and physiological responses to tiger competition in Rajaji Tiger Reserve, India

1.O_LIApex predators have critical roles in maintaining the structure of ecosystem functioning by controlling intraguild subordinate populations. Such dominant-subordinate interactions involve agonistic interactions including direct (death/displacement) or indirect (physiological and/or health implications) impacts on the subordinates. As these indirect effects are often mediated through physiological processes, it is important to quantify such responses for better understanding of population parameters. C_LIO_LIWe used a well-known sympatric large carnivore intraguild system involving tiger (Panthera tigris) and leopard (Panthera pardus) to understand the dietary and physiological responses under a spatio-temporal gradient of tiger competition pressures in Rajaji Tiger Reserve (RTR), a major source tiger population of the western Terai-Arc Landscape, India between 2015-2020. The park provided a natural experimental set-up for tiger competition with the eastern part (ERTR) having high tiger density and the western (WRTR) part with functionally no competition from tigers. C_LIO_LIWe conducted systematic faecal sampling in the winters of 2015 and 2020 from ERTR and WRTR to assess diet and physiological measures. Analyses of leopard-confirmed faeces suggest a dietary-niche separation as a consequence of tiger competition. In 2020, we found increased occurrence of large-bodied prey species without tiger competition in WRTR. Physiological measures followed the dietary responses where leopards with large-sized prey in diet showed higher fT3M and lower fGCM measures in WRTR. In contrast, ERTR leopards showed lower levels of fT3M as well as fGCM in 2020, possibly due to intense competition from tigers. Overall, these pattens strongly indicate a physiological cost of sympatry where competition with dominant tigers resulted in elevated nutritional stress. C_LIO_LIThe combination of the natural habitat providing unique experimental setup, spatio-temporal sampling strategy and multidisciplinary approaches provide critical conservation perspectives for leopards, particularly in the context of recent increase in tiger numbers across India. We recommend expansion of leopard monitoring and population estimation efforts to buffers, developing appropriate plans for human-leopard conflict mitigation and intensive efforts to understand leopard population dynamics patterns to ensure their persistence during the ongoing Anthropocene. C_LI

physiology↗

bioRxiv2022

What drives prey selection? Assessment of tiger food habits across the Terai-Arc landscape, India

Large carnivores strongly shape ecological interactions within their respective ecosystems, but experience significant conflicts with human across their range due to their specific ecological resource requirements. The tiger (Panthera tigris) typifies the challenges faced by the large carnivore communities globally. India retains majority of the global tiger population with significant numbers outside protected areas (PAs) that are involved in conflicts from livestock predation and human/tiger death. To understand the prey selection patterns and spatio-temporal patterns of livestock predation-related conflict issues we investigated tiger food habits across the Indian part of the Terai-Arc Landscape (TAL), a globally-important tiger conservation landscape in India. We used 510 genetically-confirmed tiger faeces collected across the landscape and ascertained 10 wild and livestock as major prey species. Large-bodied species (sambar, swamp deer, nilgai, chital, wild pig and livestock) comprised ~94% of tiger diet, with sambar, chital and livestock were the major prey species. Habitat-specific (Shivalik-Bhabar and Terai) analyses show significantly different pattern of prey selections determined by abundance and prey body weight. Results also suggest that PA and non-PAs of Terai habitat are more prone to livestock depredation-related conflicts, and careful management interventions and community involvements are required to reduce such threats. We suggest long-term plans including population estimation of tigers and prey outside PAs, reducing grazing pressures and cattle enumeration, detailed investigation of tiger deaths etc. to ensure future tiger sustainability across this habitat.

ecology↗

bioRxiv2022

Gamma (γ)-radiation stress response of the cyanobacterium Anabaena sp. PCC7120: Regulatory role of LexA and photophysiological changes

High radioresistance of the cyanobacterium, Anabaena sp. PCC7120 has been attributed to efficient DNA repair, protein recycling, and oxidative stress management. However, the regulatory network involved in these batteries of responses remains unexplored. In the present study, the role of a global regulator, LexA in modulating gamma ({gamma})-radiation stress response of Anabaena was investigated. Comparison of the cytosolic proteome profiles upon {gamma}-radiation in recombinant Anabaena strains, AnpAM (vector-control) and AnlexA+ (LexA-overexpressing), revealed 41 differentially accumulated proteins, corresponding to 29 distinct proteins. LexA was found to be involved in the regulation of 27 of the corresponding genes based on the presence of AnLexA-Box, EMSA, and/or qRT-PCR studies. The majority of the regulated genes were found to be involved in C-assimilation either through photosynthesis or C-catabolism and oxidative stress alleviation. Photosynthesis, measured in terms of PSII photophysiological parameters and thylakoid membrane proteome was found to be affected by {gamma}-radiation in both AnpAM and AnlexA+ cells, with LexA affecting them even under control growth conditions. Thus, LexA functioned as one of the transcriptional regulators involved in modulating {gamma}-radiation stress response in Anabaena. This study could pave the way for a deeper understanding of the regulation of {gamma}-radiation-responsive genes in cyanobacteria at large. HighlightsO_LI{gamma}-radiation alters PSII photophysiology and thylakoid proteome profile in Anabaena. C_LIO_LILexA modulates the cytosolic and thylakoid proteome of Anabaena under {gamma}-radiation. C_LIO_LILexA functions as one of the regulators of radiation-responsive genes in Anabaena. C_LI

molecular biology↗