Biology subjects

Majumdar, S.

Publications and source records attributed to Majumdar, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Projection Neurons from Infralimbic (IL) to the Basolateral Amygdala (BLA) are Critical for the Expression of Social Familiarity induced Anxiolysis (SoFiA) in rats

Mental health is crucially linked to social behavior. Healthy social behavior involves learning to adapt emotional responses to social cues, for example learning to suppress anxiety through social familiarity, or social familiarity-induced anxiolysis (SoFiA). SoFiA is well documented and forms the basis for interpersonal therapy, however, the neural mechanisms of SoFiA are unclear. SoFiA is modeled in rats by employing the social interaction habituation (SI-hab) protocol. Using SI-hab protocol, it has been determined that SoFiA represents social safety learning, which requires both anxiogenic stimulus and social familiarity during training sessions (5-6 daily SI sessions), and SoFiA expression is dependent on infralimbic subdivision (IL) of the ventromedial prefrontal cortex and the basolateral amygdala (BLA). Here we investigated the role of IL in SoFiA acquisition and expression, using chemogenetics to inhibit IL neurons. Male Wistar rats received bilateral viral injections targeting the IL or BLA and left undisturbed for 5-7 weeks to allow for viral expression. We chemogenetically inhibited via low doses of ip. clozapine-N-oxide (CNO) either the IL, the BLA, or the projections neurons from the IL to the BLA during expression of SoFiA in rats. We found that projection neurons from IL to the BLA are critical for the recovery SI behavior from the attenuation caused by the bright light (expression of SoFiA). Furthermore, CNO inhibited IL neurons with projections to the BLA and there were no off target effects of CNO on the behavioral measures. These results suggest an essential role of the IL-BLA pathway in social safety learning.

neuroscience↗

bioRxiv2026

Non-canonical proteoforms of the human fusiform gyrus in Alzheimers disease

For a long time, the protein coding potential of our genome was underestimated. Only 2% of the genome was thought to be coding for the protein while the rest was called non-coding and junk. The two main sources of biasness which resulted in underestimation were prioritising conservation and length of the open reading frames (ORFs). But recent Ribo-seq studies and high throughput quantitative proteomics studies have shown that many ORFs previously annotated as non-coding are actually getting translated into proteins and these non-canonical proteins do have certain biological functions. These findings have added more parameter perspectives to look from about different diseases. This study aims to understand translation dynamics of these proteins encoded from non-canonical ORFs in neurological disorders affecting cognitive functions specifically targeting fusiform gyrus which is linked with face recognition and anime associations which are crucial symptoms in neurological disorders. This study uses transcriptomics and proteomics analysis to understand transcriptional and translational dynamics of ncORFs. A patient cohort from the Banner Sun Health Research Institute cohort is used, corresponding RNA-seq data and Quantitative MS/MS proteomics data published in different studies are used. A custom-made protein search database was created using transcriptomics tools like STAR, StringTie and Salmon to filter out expressed ncORFs within the non-coding region and not annotated as protein coding in either GENCODE or UniProt annotations. The custom ncORF-database was then later used in proteomics analysis as search space along with the canonical proteins. The entire comprehensive analysis has resulted in identification of 22,135 ncORF-encode proteins (ncPs) and out of which 67 are differentially expressed across different neurological conditions based on the | log2FC | >1 & p.adj < 0.05 criteria. The study highlights new molecular players which might be the missing links of known mechanisms.

bioinformatics↗

bioRxiv2026

Distinct activation mechanisms underlie ligand efficacy at a GPCR

Ligands that bind to the same G protein-coupled receptor (GPCR) can produce widely different levels of signaling. These differences in efficacy are central to pharmacology, yet how a receptor sequence determines signaling level remains incompletely understood. Here we develop a deep mutational pharmacology approach to measure how each residue in the -opioid receptor (OR) shapes responses to 15 opioids, yielding ~400,000 measurements of variant effects on signaling and expression, including full concentration-response series for three agonists. Mutational effects on potency are strongest near the orthosteric pocket, whereas effects on efficacy extend through the transmembrane core and intracellular face. Ligands share many functional determinants, but sensitivity to mutation differs with efficacy. As efficacy decreases, the residues required for signaling shift from the binding pocket towards the intracellular face; partial agonists therefore depend on residues that are dispensable for full agonists. Mutations can broadly increase receptor responses, allowing antagonists such as naloxone to produce signaling comparable to a full agonist and increasing the efficacy of partial agonist ligands. Combined mutations can also reorder the relative efficacies of ligands, showing that sequence changes reshape pharmacological differences rather than simply increasing or decreasing all responses together. These findings support a model in which ligands of different efficacy activate the receptor through distinct allosteric mechanisms which are determined by residues distributed across the receptor. Mapping these contributions across diverse ligands with deep mutational pharmacology provides a way to understand how one receptor converts molecular recognition into a range of signaling outputs.

biophysics↗

bioRxiv2026

hnRNPA1 Remodels SARS-CoV-2 Genomic G-Quadruplexes through Its UP1 Domain

The single-stranded RNA genome of SARS-CoV-2 contains several predicted G-quadruplex (G4) forming sequences. Pharmacological stabilisation of these structures has been shown to suppress viral replication, suggesting that their resolution may be required for efficient viral replication. However, the roles of host proteins in stabilization or destabilization of G4 structures have remained largely unexplored. Human hnRNPA1, one of the most abundant RNA-binding proteins in eukaryotic cells, is a G-quadruplex unfolding protein and has independently been identified as a SARS-CoV-2 genome-binding protein. However, whether it acts on the G-quadruplexes within the SARS-CoV-2 genome has not been examined. Here, we screened eight putative G-quadruplex forming sequences conserved across SARS-related coronaviruses and identified two sequences that fold into G4 structures, confirmed by circular dichroism (CD) spectroscopy and thioflavin T (ThT) fluorescence-based experiments. Furthermore, we showed that the UP1 and UP1+RGG domains of hnRNPA1 specifically bind and unfold these two viral RNA G-quadruplexes. Both UP1 and UP1+RGG unfold viral RNA G-quadruplexes to similar extent, indicating that recognition and unfolding of these viral G-quadruplexes are mediated mainly by the UP1 domain of hnRNPA1. Together, these findings identify hnRNPA1 as a host factor capable of binding and remodelling SARS-CoV-2 genomic RNA G-quadruplexes and suggest a mechanism by which the virus may exploit an abundant host protein to resolve G4 structures within its genome.

biophysics↗

bioRxiv2026

Molecular determinants of ligand recognition and efficacy in the TRPM3 voltage sensor-like domain

Transient receptor potential melastatin 3 (TRPM3) is a calcium-permeable ion channel implicated in chronic pain and developmental and epileptic encephalopathies. The voltage sensor-like domain (VSLD) is a major site of pharmacological modulation, but the molecular determinants of ligand recognition and efficacy remain incompletely understood. Here we combine cryo-electron microscopy, molecular dynamics simulations, mutagenesis, and medicinal chemistry to investigate the interactions of TRPM3 with the inhibitors isosakuranetin, maprotiline, and diclofenac. We show that structurally diverse ligands occupy a common VSLD cavity but engage distinct interaction networks. Functional and computational analyses identify ligand-specific residue dependencies and support a halogen bond between diclofenac and D947 that contributes to inhibitor potency. Furthermore, esterification or amidation of the diclofenac carboxylate converts inhibition into potentiation, and mutagenesis and molecular dynamics simulations support partially overlapping VSLD configurations associated with these opposing effects. Together, these findings establish the TRPM3 VSLD as an adaptable allosteric pocket in which ligand-specific interactions shape recognition, potency, and efficacy.

biophysics↗

bioRxiv2026

Dendrimer Delivered shRNA Targeting the CCL20-CCR6 Axis Suppresses Complement-Mediated Microglial Synaptic Pruning and Ameliorates Chronic Neuroinflammation After Repetitive Traumatic Brain Injury

Repetitive traumatic brain injury (rTBI) induces persistent microglial activation and chronic neuroinflammation, yet the upstream signals driving long-term synaptic injury remain unclear. In this study, we identify the CCL20-CCR6 chemokine axis as a critical regulator of sustained microglial activation and complement-dependent synaptic loss after rTBI. Proteomic profiling at 30 days post-injury (dpi) showed broad normalization of complement-linked inflammatory and synaptic pathways in the cortex and hippocampus, underscoring a mechanistic link between chemokine signaling, microglial activation, and synaptic vulnerability. To therapeutically target this axis, we developed a dendrimer-based shRNA platform (shCombo-DPX) that simultaneously silences CCL20 and CCR6. Intranasal and intravenous delivery in rTBI mice effectively reduced CCL20-CCR6 expression, attenuated chronic microgliosis and astrogliosis, and suppressed complement activation. Treatment limited microglial synaptic engulfment, preserved synaptic proteins, restored BDNF levels, and improved motor, anxiety-related, and cognitive outcomes. In microglia-neuron coculture systems, CCL20 silencing reduced LPS-induced complement signaling and prevented synaptic loss, neuronal apoptosis, and BDNF depletion. Conversely, exposure to recombinant CCL20 induced dendritic degeneration, caspase-3 activation, microglial reactivity, complement dysregulation, and synaptic injury both in vitro and in vivo. Collectively, these findings establish CCL20-CCR6 as a key upstream driver of chronic complement-mediated synaptic degeneration after rTBI and support dendrimer-delivered shRNA therapy as a targeted strategy to mitigate long-term neurodegeneration.

neuroscience↗

bioRxiv2026

Characterisation of an evolutionarily conserved RNaseH-like domain in a domesticated transposase-derived protein

The RNase-H fold is an ancient protein fold found in diverse nucleases that is characterised by a conserved structural core (five {beta} strands and helices), canonical DDE/D catalytic residues and catalytic mechanism. This study focuses on the evolutionary conservation of the RNaseH-like domain in the transposase-derived THAP9 family among different taxonomic groups. Phylogenetic analysis demonstrates that the structural framework required for catalysis has been maintained over the course of evolution, while other peripheral regions have undergone lineage-specific diversification. This is exemplified by a Lys residue, which is conserved across mammals, can be structurally superposed on a catalytic Asp residue found in active transposases, but is not important for DNA integration. Further, the importance of conserved motifs (YREK and YKEFR motifs) near the THAP9 catalytic residues are confirmed biochemically by performing site directed mutagenesis followed by functional assays which demonstrate that substitution mutants have decreased ability to integrate DNA. Overall, these results emphasize that DNA integration activity is controlled by interactions with several structural elements rather than by individual catalytic residues.

biochemistry↗

bioRxiv2026

Predicting pain location from resting-state brain fMRI

Low back pain is a prevalent issue with few reliable treatments. Although there is great variation in clinical presentation within the low back pain population, little is known about the neurobiological mechanisms underlying these differences. In this study, we sought to stratify chronic low back pain patients (N = 275) into phenotypes characterized by correlated patterns of resting-state brain activity and sensory abnormalities (pain, numbness, and pins and needles) indicated on hand-drawn body maps. Our cross-decomposition analysis yielded phenotypes that resemble previously documented mechanistic pain types, revealing distinct brain connectivity patterns associated with different clinical presentations. Our model was then used to predict pain body maps from fMRI data in a small novel dataset of chronic pain subjects, suggesting that these relationships may generalize to other chronic pain conditions. Our results support the utility of resting-state fMRI in understanding the heterogeneity of chronic pain, which may be leveraged to develop more targeted pain treatments.

neuroscience↗

bioRxiv2026

Discovery and dynamic pharmacology of μ-opioid receptor positive allosteric modulators

Opioid agonists such as morphine and fentanyl exert analgesic effects by binding and activating the {micro}-opioid receptor ({micro}OR), yet agonism of the {micro}OR causes a slate of serious side effects. {micro}OR-mediated addiction and respiratory depression are the major causes of the current opioid overdose crisis, largely driven by the explosion in illicit use of fentanyl, a potent opioid receptor full agonist. Given these serious side effects (and high resulting societal cost), molecules that act as analgesics with distinct mechanisms of action are of great interest. Positive allosteric modulators (PAMs) of the {micro}OR have the potential to avoid many off-target side effects of conventional opioid orthosteric agonists by enhancing the signaling properties of natural opioid peptide systems. We used a DNA-encoded chemical library screening approach to selectively discover active-state-specific {micro}OR PAMs. Two out of 3 selected prospective PAMs displayed the anticipated enhancement in agonist activity. The most effective of these compounds enhanced the activity of all orthosteric opioid agonists tested, including the native opioid peptide met-enkephalin. Little is known about the underlying dynamic basis of allosteric modulation of Family A GPCRs like the {micro}OR. To that end, we used single-molecule fluorescence resonance energy transfer experiments to detail the impact that our novel {micro}OR PAM has on the dynamic activation behavior of a key region on the intracellular face of the receptor. Our results here provide both a new chemical scaffold that acts as a {micro}OR PAM and detailed pharmacological and dynamic insights into its mechanism of action.

biophysics↗

bioRxiv2026

Can Antisense lncRNA bind to the product of its sense pair?

Long non-coding RNAs (lncRNAs) account for a major proportion of the transcriptional output in complex organismal genomes. Their emergence as auxiliary regulators of gene expression as well as their roles in metastasis and cancer progression has put them in the limelight. LncRNAs perform multitudes of functions and often moonlight as regulators, scaffolds and guides. Most lncRNAs are cell and tissue specific and can act as markers for diseases as well as targets for therapeutic interventions. LncRNAs are also known to make use of higher order structures such as G-quadruplexes (G4) to facilitate complex functions and interactions. THAP9-antisense1 (AS1) is a lncRNA coding gene (recently annotated by Ensembl) that codes for 12 lncRNA transcripts and has been implicated in many disease pathologies like gastric cancer, spontaneous neutrophil apoptosis, hepatocellular carcinoma, and the progression of oesophageal cancer. It is the antisense gene pair of the THAP9 gene ( a transposase derived gene) with which it shares a promoter. THAP9-AS1 has been reported to be dysregulated during stress and several cancers. However, the exact role of the lncRNA is not well understood. Bioinformatics driven strategies are used to identify putative quadruplex forming sequences (PQSs) within the lncRNA THAP9-AS1. The identified PQSs are further validated using biophysical, spectroscopic and molecular biology driven techniques. The importance of each G-tract in the formation of a particular RNA G-quadruplex (rG4) is studied via the investigation of several deletion mutants. The findings demonstrate the rG4 forming potential of the identified PQSs within THAP9-AS1.

biochemistry↗

bioRxiv2025

Dynamic regulation of a domesticated DNA transposon-derived gene, in human germline and early embryonic development

Embryonic development requires precise transcriptional regulation to guide transitions from totipotency to pluripotency and lineage specification. Transposable element (TE) derived genes are increasingly recognised as regulators of these processes, but the role of DNA transposon-derived factors remains poorly understood. Here, we investigate human embryogenesis, primordial germ cell (PGC) development, and gametogenesis, using bulk and single-cell transcriptomic and epigenomic datasets. We observe that THAP9, a domesticated DNA transposable element-derived gene, is selectively enriched in PGCs, but transiently silenced in somatic lineages. Moreover, the gene exhibits lineage-specific expression during pre-implantation development, peaking at the zygote stage, transiently paused during cleavage, reactivated at the morula, and remains enriched in trophectoderm and embryonic stem cells but repressed in primitive endoderm and epiblast. Interestingly, THAP9 is dynamically regulated across gametogenesis, with prominent expression in spermatids and germinal vesicle oocytes. Epigenomic profiling revealed progressive chromatin remodelling, including early bivalency and enhancer activation, consistent with roles in transcriptional reprogramming. These findings identify THAP9 as a germline-enriched, developmentally regulated gene with sex-specific functions in gametogenesis and pluripotency, advancing our understanding of how domesticated transposon-derived genes contribute to human reproduction and embryogenesis

developmental biology↗

bioRxiv2025

Non-invasive detection of local microstructural damage in tendonvia Diffusion Tensor MRI

Tendon is critical for musculoskeletal function as it transfers forces generated by muscle to bone and stores energy during movement. Impaired mechanical function in tendon limits mobility and results from fatigue-induced damage progression that outpaces the restorative processes maintaning tissue health, a phenomenom we term mechanopathology. Early and non-invasive detection of tendon mechanopathologies is vital to prevent further damage, but is lacking in the clinical space. Here, we evaluate the ability of diffusion tensor magnetic resonance imaging (DT-MRI) to detect mechanical fatigue damage in tendon, and validate our findings using histologic assessments of collagen fiber microstructure and molecular structure. We found that fatigue-induced changes in DT-MRI metrics of tendon are spatially heterogeneous, and correspond to regions with damaged collagen fiber microstructure. While secondary structures of collagen molecules were damaged by fatigue loading, they do not spatially correspond to fatigue-induced changes in DT-MRI metrics. Fatigueinduced changes in DT-MRI metrics can be partially explained by quantitative metrics of post-fatigue collagen fiber microstructure, estimating the limit of detection of DT-MRI metrics to fatigue-induced damage in tendon. Our findings indicate that DT-MRI metrics are sensitive to fatigue-induced local damage in tendon, supporting the potential of DT-MRI as a non-invasive and translatable tool to clinically detect mechanopathologies in tendon.

bioengineering↗

bioRxiv2025

Differential effects of sodium on agonist-induced conformational transitions and signaling at μ and κ opioid receptors

Sodium ions are classically conceptualized as negative allosteric modulators for G protein coupled receptors (GPCRs), although there have been reports of either positive allosteric modulation or no effect of sodium on GPCR function. Here we identified opposing actions of sodium on the and {kappa} opioid receptors. We utilized a variety of methods including radioligand binding, real-time conformational monitoring of transitions using bioluminescence resonance energy transfer and signaling assays using the TRUPATH resource. At the receptors, sodium behaved as a negative allosteric modulator of binding, conformational transitions and signaling. Intriguingly, bitopic agonists were unaffected by sodium concentrations. By contrast, at the {kappa} opioid receptor sodium negatively modulated agonist binding and positively modulated conformational transitions and signaling. Taken together, these findings support the notion that the differential sensitivities to sodium concentrations will result in opposing effects on cell surface and intracellular signaling.

neuroscience↗

bioRxiv2025

Non-Equilibrium Snapshots of Ligand Efficacy at the μ-Opioid Receptor

Distinct ligands for the same G-protein coupled receptor (GPCR) activate intracellular signaling partners to varying extents, but the molecular mechanisms driving these differences remains elusive. Hypothesizing that such differences in signaling efficacy may be captured structurally in intermediate states under non-equilibrium conditions, we implemented a time-resolved (TR) cryo-EM approach to visualize the GTP-induced activation of the Gi{beta}{gamma} heterotrimer by the -opioid receptor (MOR) bound to three ligands displaying partial, full, or super-agonism on the receptor. We resolved ensembles of conformational states along the G-protein activation pathway, including a previously unobserved intermediate state that enabled us to visualize receptor dynamics as a function of bound ligand. The results demonstrate ligand-dependent differences in state occupancy and conformational stability, with higher ligand efficacy correlating with increased dynamics of the receptors transmembrane (TM) helices 5 and 6. Furthermore, we identify key mechanistic differences in the GTP-induced activation of Gi compared to Gs that likely underlie their distinct activation kinetics. Corroborated by molecular dynamics (MD) simulations, these findings provide a dynamic structural landscape of GPCR-G-protein interactions for ligands of different efficacy and suggest partial agonists may produce a kinetic trap during G-protein activation.

pharmacology and toxicology↗

bioRxiv2025

Transcriptional Landscape of THAP9 across Oligodendrocyte Developmental Stages: Molecular Mechanisms and Network Analysis

Oligodendrocyte maturation and myelination are critical processes in human neurodevelopment, and their dysregulation is linked to numerous neurological disorders. While model organisms have provided insight into these processes, human-specific regulatory mechanisms remain poorly understood. This study investigated human THAP9, a protein homologous to the Drosophila P-element transposase, whose function in oligodendrocytes remains unknown. An analysis of publicly available RNA-sequencing data and H3K27ac ChIP-sequencing data from oligodendrocyte progenitor cells (OPCs) and mature oligodendrocytes (MOs) revealed significant upregulation of THAP9 during oligodendrocyte maturation. Co-expression analysis demonstrated a strong correlation with established markers of oligodendrocyte development, including myelin-associated genes (MOG, MBP) and key transcriptional regulators (PDGFRA, SOX5, SOX6, SOX11). THAP9 lacks homologues in mice, highlighting potential human-specific mechanisms in oligodendrocyte development and emphasising the importance of studying species-specific factors in neurodevelopment. Our findings suggest that THAP9 is a novel human-specific regulator of oligodendrocyte maturation and opens new avenues for studying myelination disorders.

genomics↗

bioRxiv2024

A Novel Actinobacteria-Specific Ribosome Hibernation Factor in Mycobacterium tuberculosis

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), persists within its host for long periods. Treatment of TB requires prolonged administration of antibiotics, some of which target Mtb ribosomes, the protein synthesizing machine of the cell. We determined high-resolution cryo-EM structures of Mtb ribosomes obtained from biofilms under zinc-depleted conditions that are expected to induce ribosome hibernation. In these structures, in addition to finding the Mtb homolog of the hibernation promoting factor Mpy that binds to the decoding center in the small ribosomal subunit, we discovered an actinobacteria-specific protein, previously of unknown function, bound in the nascent polypeptide-exit tunnel (NPET) within the large ribosomal subunit. We refer to this NPET-bound protein as a actinobacteria-specific ribosome tunnel occlusion factor (RTOF). RTOF is found with vacant or E-tRNA-bound 70S ribosomes, but not in actively translating Mtb ribosomes, suggesting that its binding coincides with ribosome hibernation. RTOF makes strong interactions through the entire stretch of NPET extending up to the peptidyl-transferase center (PTC), such that it would block the passage of nascent polypeptide chain. The highly conserved FRRKSG motif of RTOF also interferes with accommodation of the formyl-methionyl moiety of initiator fMet-tRNAfMet in the conformation required for translation initiation. A molar excess of mRNA and initiator fMet-tRNAfMet displaces RTOF by triggering a significant alteration to the conformation of FRRKSG motif, which suggests how RTOF-bound hibernating ribosomes can be reactivated under optimal cellular conditions. The presence of RTOF would interfere with the binding of PTC-targeting drugs, such as macrolides, lincosamides, and oxazolidines, thereby maintaining a drug-free pool of hibernating Mtb ribosomes.

microbiology↗

bioRxiv2024

Cxcl10 is required for survival during SARS-CoV-2 infection in mice

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic, remains endemic worldwide [~]5 years since the first documented case. Severe COVID-19 is widely considered to be caused by a dysregulated immune response to SARS-CoV-2 within the respiratory tract. Circulating levels of the chemokine CXCL10 are strongly positively associated with poor outcome; however, its precise role in pathogenesis and its suitability as a therapeutic target have remained undefined. Here, we challenged 4-6 month old C57BL/6 mice genetically deficient in Cxcl10 with a mouse-adapted strain of SARS-CoV-2. Infected male, but not female, Cxcl10-/- mice displayed increased mortality compared to wild type controls. Histopathological damage, inflammatory gene induction and virus load in the lungs of male mice 4 days post infection and before death were not broadly influenced by Cxcl10 deficiency. However, accumulation of B cells and both CD4+ and CD8+ T cells in the lung parenchyma of infected mice was reduced in the absence of Cxcl10. Thus, during acute SARS-CoV-2 infection, Cxcl10 regulates lymphocyte infiltration in the lung and confers protection against mortality. Our preclinical model results do not support targeting CXCL10 therapeutically in severe COVID-19.

immunology↗

bioRxiv2024

Mechanism of host cell invasion by Leishmania through KMP-11 mediated cholesterol-transport and membrane phase transition

The first step of successful infection by any intracellular pathogen relies on its ability to invade its host cell membrane. However, the detailed structural and molecular understanding underlying lipid membrane modification during pathogenic invasion remains unclear. In this study, we show that a specific Leishmania donovani (LD) protein, KMP-11, forms oligomers that bridge LD and host macrophage (M{Phi}) membranes. This KMP-11 induced interaction between LD and M{Phi} depends on the variations in cholesterol (CHOL) and ergosterol (ERG) contents in their respective membranes. These variations are crucial for the subsequent steps of invasion, including (a) the initial attachment, (b) CHOL transport from M{Phi} to LD, and (c) detachment of LD from the initial point of contact through a liquid ordered (Lo) to liquid disordered (Ld) membrane-phase transition. To validate the importance of KMP-11, we generated KMP-11 depleted LD, which failed to attach and invade host M{Phi}. Through tryptophan-scanning mutagenesis and synthesized peptides, we developed a generalized mathematical model, which demonstrates that the hydrophobic moment and the symmetry sequence code at the membrane interacting protein domain are key factors in facilitating the membrane phase transition and, consequently, the host cell infection process by Leishmania parasites.

biophysics↗