Biochemical and Biophysical Research Communications, Journal Year: 2025, Volume and Issue: unknown, P. 151828 - 151828
Published: April 1, 2025
Language: Английский
Cell Reports, Journal Year: 2024, Volume and Issue: 43(3), P. 113965 - 113965
Published: March 1, 2024
G3BP1/2 are paralogous proteins that promote stress granule formation in response to cellular stresses, including viral infection. The nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inhibits assembly and interacts with via an ITFG motif, residue F17, the N protein. Prior studies examining impact G3PB1-N interaction on SARS-CoV-2 replication have produced inconsistent findings, role this pathogenesis is unknown. Here, we use structural biochemical analyses define residues required for G3BP1-N structure-guided mutagenesis selectively disrupt interaction. We find N-F17A mutation causes highly specific loss G3BP1/2. fails inhibit cells, has decreased replication, pathology vivo. Further mechanistic indicate N-F17-mediated promotes infection by limiting sequestration genomic RNA (gRNA) into granules.
Language: Английский
Citations
25
Cell Reports Medicine, Journal Year: 2024, Volume and Issue: 5(2), P. 101379 - 101379
Published: Feb. 1, 2024
The high failure rate of clinical trials in Alzheimer's disease (AD) and AD-related dementia (ADRD) is due to a lack understanding the pathophysiology disease, this deficit may be addressed by applying artificial intelligence (AI) "big data" rapidly effectively expand therapeutic development efforts. Recent accelerations computing power availability big data, including electronic health records multi-omics profiles, have converged provide opportunities for scientific discovery treatment development. Here, we review potential utility AI approaches data disease-modifying medicines AD/ADRD. We illustrate how tools can applied AD/ADRD drug pipeline through collaborative efforts among neurologists, gerontologists, geneticists, pharmacologists, medicinal chemists, computational scientists. open science expedite therapeutics other neurodegenerative diseases.
Language: Английский
Citations
20
Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)
Published: April 26, 2023
Viruses mimic host short linear motifs (SLiMs) to hijack and deregulate cellular functions. Studies of motif-mediated interactions therefore provide insight into virus-host dependencies, reveal targets for therapeutic intervention. Here, we describe the pan-viral discovery 1712 SLiM-based using a phage peptidome tiling intrinsically disordered protein regions 229 RNA viruses. We find mimicry SLiMs be ubiquitous viral strategy, novel proteins hijacked by viruses, identify pathways frequently deregulated motif mimicry. Using structural biophysical analyses, show that mimicry-based have similar binding strength bound conformations as endogenous interactions. Finally, establish polyadenylate-binding 1 potential target broad-spectrum antiviral agent development. Our platform enables rapid mechanisms interference identification which can aid in combating future epidemics pandemics.
Language: Английский
Citations
34
Mass Spectrometry Reviews, Journal Year: 2024, Volume and Issue: unknown
Published: May 14, 2024
Abstract Protein–protein interactions (PPIs) are essential for numerous biological activities, including signal transduction, transcription control, and metabolism. They play a pivotal role in the organization function of proteome, their perturbation is associated with various diseases, such as cancer, neurodegeneration, infectious diseases. Recent advances mass spectrometry (MS)‐based protein interactomics have significantly expanded our understanding PPIs cells, techniques that continue to improve terms sensitivity, specificity providing new opportunities study diverse systems. These differ depending on type interaction being studied, each approach having its set advantages, disadvantages, applicability. This review highlights recent enrichment methodologies interactomes before MS analysis compares unique features specifications. It emphasizes prospects further improvement potential applications advancing knowledge contexts.
Language: Английский
Citations
10
Science Advances, Journal Year: 2024, Volume and Issue: 10(22)
Published: May 29, 2024
Surface plasmons have proven their ability to boost the sensitivity of mid-infrared hyperspectral imaging by enhancing light-matter interactions. phonons, a counterpart technology plasmons, present unclear contributions imaging. Here, we investigate this developing plasmon-phonon system that uses asymmetric cross-shaped nanoantennas composed stacked materials. The phonon modes within system, controlled light polarization, capture molecular refractive index intensity and lineshape features, distinct from those observed with enabling more precise sensitive molecule identification. In deep learning-assisted demonstration severe acute respiratory syndrome coronavirus (SARS-CoV), phonons exhibit enhanced identification capabilities (230,400 spectra/s), facilitating de-overlapping observation spatial distribution two mixed SARS-CoV spike proteins. addition, demonstrates increased accuracy (93%), heightened sensitivity, detection limits (down monolayers). These findings extend polaritonics imaging, promising applications in imaging-guided screening pharmaceutical analysis.
Language: Английский
Citations
9
Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)
Published: Feb. 27, 2024
Candidalysin, a cytolytic peptide toxin secreted by the human fungal pathogen Candida albicans, is critical for pathogenesis. Yet, its intracellular targets have not been extensively mapped. Here, we performed high-throughput enhanced yeast two-hybrid (HT-eY2H) screen to map interactome of all eight Ece1 peptides with their direct protein and identified list potential interacting proteins, some which were shared between peptides. CCNH, regulatory subunit CDK-activating kinase (CAK) complex involved in DNA damage repair, was as one host candidalysin. Mechanistic studies revealed that candidalysin triggers significantly increased double-strand breaks (DSBs), evidenced formation γ-H2AX foci colocalization CCNH γ-H2AX. Importantly, binds directly activate CAK inhibit repair pathway. Loss alleviates DSBs under treatment. Depletion candidalysin-encoding gene fails induce stimulates upregulation murine model oropharyngeal candidiasis. Collectively, our study reveals acts hijack canonical pathway targeting promote infection.
Language: Английский
Citations
8
npj Science of Food, Journal Year: 2024, Volume and Issue: 8(1)
Published: March 30, 2024
Language: Английский
Citations
8
European Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 103(2), P. 151393 - 151393
Published: Jan. 24, 2024
The ability of a pathogen to survive and cause an infection is often determined by specific interactions between the host proteins. Such can be both intra- extracellular may define outcome infection. There are range innovative biochemical, biophysical bioinformatic techniques currently available identify protein-protein (PPI) pathogen. However, complexity diversity host-pathogen PPIs has led development several high throughput (HT) that enable study multiple at once and/or screen samples same time, in unbiased manner. We review here major HT laboratory-based technologies employed for host-bacterial interaction studies.
Language: Английский
Citations
6
PLoS Biology, Journal Year: 2024, Volume and Issue: 22(9), P. e3002767 - e3002767
Published: Sept. 24, 2024
Interferons (IFNs) play a crucial role in the regulation and evolution of host–virus interactions. Here, we conducted genome-wide arrayed CRISPR knockout screen presence absence IFN to identify human genes that influence Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. We then performed an integrated analysis interacting with SARS-CoV-2, drawing from selection 67 large-scale studies, including our own. identified 28 high relevance both genetic studies Disease 2019 (COVID-19) patients functional screens cell culture, many related pathway. Among these was IFN-stimulated gene PLSCR1 . did not require induction restrict SARS-CoV-2 contribute signaling. Instead, specifically restricted spike-mediated entry. The PLSCR1-mediated restriction alleviated by TMPRSS2 overexpression, suggesting primarily restricts endocytic entry route. In addition, recent variants have adapted circumvent barrier via currently undetermined mechanisms. Finally, investigate effects present humans discuss association between severe COVID-19 reported recently.
Language: Английский
Citations
6
Circulation Research, Journal Year: 2023, Volume and Issue: 132(10), P. 1374 - 1386
Published: May 11, 2023
COVID-19 is an infectious disease caused by SARS-CoV-2 leading to the ongoing global pandemic. Infected patients developed a range of respiratory symptoms, including failure, as well other extrapulmonary complications. Multiple comorbidities, hypertension, diabetes, cardiovascular diseases, and chronic kidney are associated with severity increased mortality COVID-19. infection also causes complications, myocarditis, myocardial injury, heart arrhythmias, acute coronary syndrome, venous thromboembolism. Although variety methods have been many clinical trials launched for drug repositioning COVID-19, treatments that consider manifestations comorbidities specifically limited. In this review, we summarize recent advances in experimental repositioning, high-throughput screening, omics data-based, network medicine-based computational particular attention on those We discuss prospective opportunities potential repurposing drugs treat complications
Language: Английский
Citations
16