Syntaxin11 Deficiency Inhibits CRAC Channel Priming To Suppress Cytotoxicity And Gene Expression In FHLH4 Patient T Lymphocytes.

CRAC channels enable calcium entry from the extracellular space in response to a variety of stimuli and are crucial for gene expression and granule exocytosis in lymphocytes. Here we find that Syntaxin11, a Q-SNARE, associated with FHLH4 disease in human patients, directly binds Orai1, the pore forming subunit of CRAC channels. Syntaxin11 depletion strongly inhibited SOCE, CRAC currents, IL-2 expression and cytotoxicity in cell lines and FHLH4 patient T lymphocytes.

Transcriptional regulation of hormone signalling genes in black pepper in response to Phytophthora capsici.

Introduction: Black pepper (Piper nigrum L.) is a non-model spice crop of significant agricultural and biological importance. The 'quick wilt' disease caused by the oomycete Phytophthora capsici is a major threat, leading to substantial crop loss.

Sensing volatiles throughout the body: geographic- and tissue-specific olfactory receptor expression in the fig wasp.

An essential adaptive strategy in insects is the evolution of olfactory receptors (ORs) to recognize important volatile environmental chemical cues. Our model species, Ceratosolen fusciceps, a specialist wasp pollinator of Ficus racemosa, likely possesses an OR repertoire that allows it to distinguish fig-specific volatiles in highly variable environments. Using a newly assembled genome-guided transcriptome, we annotated 63 ORs in the species and reconstructed the phylogeny of Ceratosolen ORs in conjunction with other hymenopteran species.

Computational analysis of human gut microbial prolyl oligopeptidases (POPs) reveal candidate genes as therapeutics for celiac disease.

Celiac disease (CD) is a common autoimmune disorder in which the patients are unable to digest gluten, which is present in foods made up of wheat, barley and rye. Whilst diagnosis happens late in 80% of the cases, avoidance of such foods appears to be the common solution. Alternative management strategies are required for the patients and their families since CD is also genetically carried over.

Computational Analysis of the Accumulation of Mutations in Therapeutically Important RNA Viral Proteins During Pandemics with Special Emphasis on SARS-CoV-2.

Single stranded RNA viruses are primary causative agents for pandemics, causing extensive morbidity and mortality worldwide. A pivotal question in pandemic preparedness and therapeutic intervention is what are the specific mutations which are more likely to emerge during such global health crises? This study aims to identify markers for mutations with the highest probability of emergence in these pandemics, focusing on the SARS-CoV-2 spike protein, an essential and therapeutically significant viral protein, starting from sequence information from the onset of the pandemic until July 2022. Quite consistently, we observed that emerged mutations tended to demonstrate a high genetic score, which reflects high similarity of the type of codon required for translation between an amino acid and to the mutated one.

Normal Mode Analysis Elicits Conformational Shifts in Proteins at Both Proximal and Distal Regions to the Phosphosite Stemming from Single-Site Phosphorylation.

Phosphorylation, a fundamental biochemical switch, intricately regulates protein function and signaling pathways. Our study employs extensive computational structural analyses on a curated data set of phosphorylated and unphosphorylated protein pairs to explore the multifaceted impact of phosphorylation on protein conformation. Using normal mode analysis (NMA), we investigated changes in protein flexibility post-phosphorylation, highlighting an enhanced level of structural dynamism.

Interfacial residues in protein-protein complexes are in the eyes of the beholder.

Interactions between proteins are vital in almost all biological processes. The characterization of protein-protein interactions helps us understand the mechanistic basis of biological processes, thereby enabling the manipulation of proteins for biotechnological and clinical purposes. The interface residues of a protein-protein complex are assumed to have the following two properties: (a) they always interact with a residue of a partner protein, which forms the basis for distance-based interface residue identification methods, and (b) they are solvent-exposed in the isolated form of the protein and become buried in the complex form, which forms the basis for Accessible Surface Area (ASA)-based methods.

The alteration of structural network upon transient association between proteins studied using graph theory.

Proteins such as enzymes perform their function by predominant non-covalent bond interactions between transiently interacting units. There is an impact on the overall structural topology of the protein, albeit transient nature of such interactions, that enable proteins to deactivate or activate. This aspect of the alteration of the structural topology is studied by employing protein structural networks, which are node-edge representative models of protein structure, reported as a robust tool for capturing interactions between residues.

Comparative analysis of permanent and transient domain-domain interactions in multi-domain proteins.

Protein domains are structural, functional, and evolutionary units. These domains bring out the diversity of functionality by means of interactions with other co-existing domains and provide stability. Hence, it is important to study intra-protein inter-domain interactions from the perspective of types of interactions.

Integrated approaches for the recognition of small molecule inhibitors for Toll-like receptor 4.

Toll-like receptors (TLRs) are pattern recognition receptors present on the surface of cells playing a crucial role in innate immunity. One of the TLRs, TLR4, recognizes LPS (Lipopolysaccharide) as its ligand leading to the release of anti-inflammatory mediators as well as pro-inflammatory cytokines through signal transduction and domain recruitment. TLR4 homodimerizes at its intracellular TIR (Toll/interleukin-1 receptor) domain that helps in the recruitment of the TRAM/TICAM2 (TIR domain-containing adaptor molecule 2) molecule.

Draft genome sequence of an invasive plant .

L. is an invasive species of global concern. An ornamental plant originating from central America, it has now spread across natural and human-dominated habitats across tropical and subtropical regions globally.

Influence of pH on indole-dependent heterodimeric interactions between Anopheles gambiae odorant-binding proteins OBP1 and OBP4.

Insect Odorant Binding Proteins (OBPs) constitute important components of their olfactory apparatus, as they are essential for odor recognition. OBPs undergo conformational changes upon pH change, altering their interactions with odorants. Moreover, they can form heterodimers with novel binding characteristics.

Transcriptome data analysis of primary cardiomyopathies reveals perturbations in arachidonic acid metabolism.

Introduction: Cardiomyopathies are complex heart diseases with significant prevalence around the world. Among these, primary forms are the major contributors to heart failure and sudden cardiac death. As a high-energy demanding engine, the heart utilizes fatty acids, glucose, amino acid, lactate and ketone bodies for energy to meet its requirement.

A census of actin-associated proteins in humans.

Actin filaments help in maintaining the cell structure and coordinating cellular movements and cargo transport within the cell. Actin participates in the interaction with several proteins and also with itself to form the helical filamentous actin (F-actin). Actin-binding proteins (ABPs) and actin-associated proteins (AAPs) coordinate the actin filament assembly and processing, regulate the flux between globular G-actin and F-actin in the cell, and help maintain the cellular structure and integrity.

Biography of a scientist with strength, substance, sincerity and service: Late N. Srinivasan (1962-2021).

Late N. Srinivasan belongs to the GN Ramachandran lineage of protein structural analysts. His role in the advancement of the structure based understanding of signal transduction, protein kinase analyses and host-pathogen interactions both developing and using Bioinformatics tools for protein-protein interactions, protein dynamics, remote homology detection and polypeptide stereochemistry is well documented in the literature.

Structural rationale to understand the effect of disease-associated mutations on Myotubularin.

Myotubularin or MTM1 is a lipid phosphatase that regulates vesicular trafficking in the cell. The gene is mutated in a severe form of muscular disease, X-linked myotubular myopathy or XLMTM, affecting 1 in 50,000 newborn males worldwide. There have been several studies on the disease pathology of XLMTM, but the structural effects of missense mutations of MTM1 are underexplored due to the unavailability of a crystal structure.

Computational analysis of the flexibility in the disordered linker region connecting LIM domains in cysteine-glycine-rich protein.

One of the key proteins that are present in the Z-disc of cardiac tissues, CSRP3, has been implicated in dilated and hypertrophic cardiomyopathy leading to heart failure. Although multiple cardiomyopathy-related mutations have been reported to reside on the two LIM domains and the disordered regions connecting the domains in this protein, the exact role of the disordered linker region is not clear. The linker harbors a few post-translational modification sites and is expected to be a regulatory site.

Structure modelling of odorant receptor from and identification of potential repellent molecules.

Odorant receptors (ORs) are important class of proteins involved in olfactory behaviour of insects. These are GPCR-like heptahelical transmembrane proteins with inverted topology compared to GPCR and require a co-receptor (ORco) for their function. OR function can be modulated through small molecules and negative modulation can be beneficial in case of disease vectors like .

Structural modelling and dynamics of full-length of TLR10 sheds light on possible modes of dimerization, ligand binding and mechanism of action.

Toll like receptors (TLRs) play a pivotal role in innate and adaptive immunity. There are 10 TLRs in the human genome, of which TLR10 is the least characterized. Genetic polymorphism of TLR10 has been shown to be associated with multiple diseases including tuberculosis and rheumatoid arthritis.

Bioinformatics Analysis of Mutations Sheds Light on the Evolution of Dengue NS1 Protein With Implications in the Identification of Potential Functional and Druggable Sites.

Non-structural protein (NS1) is a 350 amino acid long conserved protein in the dengue virus. Conservation of NS1 is expected due to its importance in dengue pathogenesis. The protein is known to exist in dimeric and hexameric states.

Transcriptome profiling of two Moringa species and insights into their antihyperglycemic activity.

Background: Moringa concanensis Nimmo (MC), a plant that resembles Moringa oleifera Lam. (MO), has less scientific information but has traditionally been used as a medicinal plant. Moringa species have long been known for their medicinal qualities, which include antioxidant, anti-inflammatory, anticancer, and antihyperglycemic effects.

Integrative network analysis interweaves the missing links in cardiomyopathy diseasome.

Cardiomyopathies are progressive disease conditions that give rise to an abnormal heart phenotype and are a leading cause of heart failures in the general population. These are complex diseases that show co-morbidity with other diseases. The molecular interaction network in the localised disease neighbourhood is an important step toward deciphering molecular mechanisms underlying these complex conditions.

Computational tools to study RNA-protein complexes.

RNA is the key player in many cellular processes such as signal transduction, replication, transport, cell division, transcription, and translation. These diverse functions are accomplished through interactions of RNA with proteins. However, protein-RNA interactions are still poorly derstood in contrast to protein-protein and protein-DNA interactions.