Biology subjects

Iqbal, N.

Publications and source records attributed to Iqbal, N..

8 recordsLinked to original sources

bioRxiv2026

Electrostatic Complementarity at the ClpX Substrate-EntryChannel Governs ATP-Driven Protein Unfolding

AAA+ proteases maintain proteostasis by mechanically unfolding protein substrates before degradation, yet how ATP-driven pulling is converted into productive unfolding remains poorly understood. Here, using ssrA-tagged GFP substrates spanning a range of surface charges, we show that electrostatic complementarity between the positively charged ClpX substrate-entry channel and folded substrate domains governs unfolding efficiency. Positively charged substrates unfolded inefficiently despite substrate recognition, thermal stability, ATPase activation, and pore-loop engagement comparable to negatively charged substrates. Cryo-EM structures of a positively charged substrate revealed multiple substrate-engagement states arising from electrostatic incompatibility at the ClpX substrate-entry channel, whereas negatively charged substrates formed favorable electrostatic interactions that likely stabilize partially unfolded intermediates during successive ATP-driven unfolding attempts. Together, these findings identify electrostatic complementarity as a key determinant of productive ATP-driven protein unfolding and suggest that tuning substrate or substrate-entry electrostatics provides a mechanism for regulating AAA+ protease activity.

biochemistry↗

bioRxiv2025

In silico pharmacological analysis of Tinospora cordifolia compounds targeting African swine fever virus B175L

African swine fever virus (ASFV) is a highly lethal DNA virus that suppresses the hosts immune response by establishing infection. B175L, one of its key immune evasion proteins, directly inhibits STING-mediated type I interferon (IFN-I) signaling, preventing antiviral defense activation. Thus, targeting B175L could be a promising strategy for antiviral drug development as effective ASFV inhibitors remain unidentified. In this study, we investigated the potential of the Tinospora cordifolia plants bioactive compounds to disrupt B175Ls function, restoring immune signaling. Gas chromatography-mass spectrometry (GC-MS) analysis of T. cordifolia stems methanol extract identified 124 compounds, of which 52 met SwissADME and DataWarrior criteria for drug-likeness and safety. We generated a highly accurate 3D B175L model with strong confidence scores for the structure accuracy, utilizing AlphaFold3. Virtual screening was performed using PyRx 0.8, and the top 4 ligands with binding affinities exceeding -6 kcal/mol advanced to CB-Dock2 and UCSF Chimera. Among them, Benzaldehyde, 5-bromo-2-hydroxy-, (5-trifluoromethyl-2pyridyl)hydrazone exhibited the highest binding affinity (-8.2 kcal/mol), confirming its strong interactions at the active site of B175L. Molecular dynamics (MD) simulations demonstrated the compounds stability, with root mean square deviation and fluctuation (RMSD, RMSF) indicating minimal conformational changes (<2 [A]). The compound maintained stable hydrogen bonds and hydrophobic interactions, reinforcing structural robustness. Taken together, these results clearly emphasize T. cordifolia-derived Benzaldehyde, 5-bromo-2-hydroxy-, (5-trifluoromethyl-2-pyridyl)hydrazone as a promising B175L inhibitor, advancing exploration towards effective antiviral solutions for ASFV.

bioinformatics↗

bioRxiv2025

Structural Plasticity of the Membrane-Bound Protein Degradation Assembly Supports Bacterial Adaptation to Stress

Protein degradation by AAA+ proteases is essential for bacterial adaptation to environmental stress. The membrane-bound AAA+ protease FtsH forms a large inner-membrane complex with the SPFH (Stomatin, Prohibitin, Flotillin, HflK/C) family transmembrane proteins HflK and HflC, playing a key role in bacterial recovery from aminoglycoside antibiotic stress. Recent structural studies have revealed both open, asymmetric and closed, symmetric conformations of the HflK/C assembly under different sample-preparation conditions, suggesting two distinct models for how this complex modulates FtsH proteolysis. To determine which conformation reflects the biologically active state, we engineered a disulfide-crosslinked HflK/C variant to stabilize the closed conformation and resolved its structure using high-resolution cryo-EM. Phenotypic assays showed that cells expressing either this stabilized, closed HflK/C variant or an HflK/C mutant that disrupts interactions with FtsH exhibit significantly impaired growth under aminoglycoside stress. Surprisingly, the cryo-EM structure of the FtsH*HflK/C complex from cells challenged with the aminoglycoside antibiotic tobramycin revealed a novel HflK/C arrangement, characterized by two openings on opposite sides that may facilitate substrate access to FtsH during proteotoxic stress. Together, our results suggest that both the dynamic open conformation of HflK/C and its specific interactions with FtsH are critical for adaptation to aminoglycoside-induced stress. Given the conserved structural and functional features of SPFH family members, our findings may offer a broader framework for understanding how this protein family operates under both basal and stress conditions.

biophysics↗

bioRxiv2025

Soil and water microbial communities: A source of novel antibiotics for sustainable plant disease control

Pathogenic microorganisms pose a significant threat to plant health and agricultural productivity worldwide. Herein, this study explores the potential of natural microbial communities as sources of biopesticides. We analyzed 20 soil and water samples from remote areas, isolating 121 colonies using nutrient agar. Antibacterial activity was assessed through agar diffusion, revealing that 12 colonies exhibited significant inhibitory effects against various pathogenic bacteria. Measurement of inhibition zones indicated that these colonies could produce antibiotics. Subsequently, molecular characterization with 16S rRNA and BLAST searches of 12 unidentified sequences highlighted substantial microbial diversity within the samples. This research underscores the promise of these natural microbial communities in developing biocontrol agents for managing plant diseases in greenhouse and field environments. Extraction and purification techniques could further refine these antibiotics, advancing sustainable agricultural practices.

microbiology↗

bioRxiv2023

Invariant natural killer T-cell and CD4+ T-cell derived IL22 is a regulator of epithelial-to-mesenchymal transition and extracellular matrix remodelling in perianal fistulas

Background and aimsPerianal fistulization is a challenging phenotype of Crohns disease (CD). Unravelling the cytokine networks and cellular mediators driving tissue injury in perianal CD (pCD) will help inform much needed novel treatment strategies. MethodsThe phenotype of different T-cell subsets, including unconventional lineages, such as {gamma}{delta} T-cells, MAIT and iNKT-cells in fistula tract tissue and blood samples of patients with pCD or cryptoglandular perianal fistulas was determined using multiparameter flow cytometry. Transcriptomic profiling of fistula tract tissue was performed by RNA-sequencing. ResultsCD161+ CD4+ T-cells and CD161+ CD4- CD8- iNKT-cells significantly accumulated in fistula tissue and produced interleukin-(IL)22 and IL13. Transcripts associated with epithelial-to-mesenchymal transition (EMT), extracellular matrix (ECM) remodelling, interferon-gamma, JAK-STAT and lymphocyte signalling were enriched in pCD, as well as inhibition of pathways associated with wound closure. IL22-responsive transcripts were significantly enriched in fistulas and network analysis identified IL22-mediated regulation of EMT, ECM and other inflammatory pathways. ConclusionThis study provides novel molecular and cellular insights into fistula pathogenesis, identifying IL22 producing lymphocytes as novel immune regulators of EMT and ECM dysregulation in perianal fistulas. Targeting the regulatory networks controlling IL22 producing lymphocytes may offer novel therapeutic strategies in pCD.

immunology↗

bioRxiv2023

Pericardial & Mediastinal Fat-Associated Lymphoid Clusters are rapidly activated in an alkane induced model of Systemic Lupus Erythematosus

Systemic Lupus Erythematosus (SLE) is an autoimmune disease predominated by auto-antibodies that recognise cellular components. Pleural involvement is the most common SLE-related lung disease. Natural antibodies are rapidly secreted by innate-like B cells following perturbation of homeostasis and are important in the early stages of immune activation. The serous cavities are home to large numbers of innate-like B cells present both within serous fluid and resident within fat-associated lymphoid clusters (FALCs). FALCs are important hubs for B-cell activation and local antibody secretion within the body cavities. Patients with SLE can develop anti-phospholipid antibodies and in rare situations develop alveolar haemorrhage. Utilising delivery of the hydrocarbon oil pristane in C57BL/6 mice as a model of SLE we identify a rapid expansion of pleural cavity B cells as early as day 3 after intra-peritoneal pristane delivery. Following pristane delivery, pericardial B1 B cells are proliferative, express the plasma-cell surface marker CD138 and secrete both innate and class switched antibodies highlighting that this cavity niche may play an unrecognised role in the initiation of lupus pleuritis. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=163 SRC="FIGDIR/small/549766v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@18ea5bforg.highwire.dtl.DTLVardef@23d9deorg.highwire.dtl.DTLVardef@1b48b3aorg.highwire.dtl.DTLVardef@20a133_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2022

Perception and Readiness Towards Inter-Professional Education Among Different Health Care Disciplines at Khyber Medical University Peshawar

Interprofessional learning (IPL) is an approach that teaches students diverse disciplines to communicate with each other about their professional knowledge in order to acquire a more complex one understanding of the current situation. According to WHO definition of IPE "its a process between two or more professionals learn about from, and with one another to permit effective association and enhance health outcome. The aim of this study was to measure perception and readiness towards IPE among different health care disciplines. A cross-sectional study was done with two hundred and eighteen post graduate Nursing, public health, physiotherapy, and basic medical sciences students from September,2020 to January,2021 at Khyber Medical University Peshawar Pakistan. Convenient sampling technique was used to collect data. The Readiness for Inter-Professional Learning Scale (RIPLS) and Interdisciplinary Education Perception Scale (IEPS) were used to measure the readiness and perception of students regarding inter-professional leaning. The data were analyzed using software Statistical Package for Social Science (SPSS) (Version 23). The RIPLS was completed by a total of 218 participants (response rate 100%, 61 Nursing students 28%, 51 physiotherapy students 23.4%, 53 public health students 24.3%, and 53 basic medical sciences students 24.3%). As shown in Table 1.1, the majority of respondents were male (51.4%) followed by female (48.6%). Most of the respondents were aged with a mean score of 27.92 {+/-} 3.195. Moreover, majority of respondents have experience less than 5years (75.2%) and (22.8%) has experience above than 5years. Value of perception and readiness in Shapiro-Wilk is .000 which shows that the data variable is not normally distributed. correlation of students towards interprofessional learning by applying Spearman rho test. Students perception has strong positive correlation with their readiness, p value (.000). Also students readiness has strong positive correlation with their perception towards interprofessional learning. This study was to explore the readiness and perception of students towards interprofessional education in different health care students. IPL is beneficial for students to know other professionals to work together for teamwork and collaboration and it also increase communication between different health care professional and patients.

scientific communication and education↗

bioRxiv2020

Urethral luminal epithelia are castration-insensitive progenitors of the proximal prostate

Castration-insensitive epithelial progenitors capable of regenerating the prostate are concentrated in the proximal region close to the urethra, but the identification of these cells has been limited to individual cell surface markers. Here, we use single cell RNA sequencing (scRNA-seq) to obtain a cellular anatomy of the mouse prostate and urethra and create a comparative map with the human. These data reveal that previously identified facultative progenitors marked by TROP2, Sca-1, KRT4, and PSCA are actually luminal epithelia of the urethra that extend into the proximal prostate. These mouse urethral cells are the human equivalent of previously identified club and hillock urethral cells. Castration decreases androgen-dependent prostate luminal epithelia as expected, but TROP2+ urethral luminal epithelia survive and expand into the prostate. Benign prostatic hyperplasia (BPH) has long been considered an embryonic reawakening, but the cellular origin of peri-urethral growth is unclear. We use scRNA-seq and flow cytometry to demonstrate an increase in urethral luminal epithelia within glandular nodules from patients with BPH, which are further enriched in patients treated with a 5 alpha reductase inhibitor. These data demonstrate that the putative prostate progenitors enriched by castration in the proximal prostate are an expansion of urethral luminal epithelia and that these cells may play an important role in the etiology of human BPH. Significance StatementThe prostate involutes after castration, but regrows to its original size with androgen replenishment. This observation prompted the search for a castration-insensitive prostate progenitor. Here, Joseph et al. produce a comparative cellular atlas of the prostate and urethra in the mouse vs. human, discovering an equivalent urethral luminal epithelial cell type that extends into the proximal prostatic ducts and expresses previously identified markers of facultative prostate progenitors. Urethral luminal epithelia are established before prostate budding in human and mouse development, and expand after castration in the mouse and after 5 alpha reductase inhibitor treatment in human BPH. These data suggest that luminal epithelia of the urethra are castration-insensitive cells of proximal ducts that may act as progenitors in human BPH.

cell biology↗