Immunomodulatory M3 Protein of Murine Herpesvirus 68: Chemokine Binding Affinity, Molecular Recognition and Stability
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB47401 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Here, we report a CRISPR/Cas12k-transposon-assisted genome engineering (CTAGE) method that allows for high-throughput site-specific mutagenesis in microbial genomes. Exploiting the powerful CTAGE technique, we construct a site-specific transposon mutant library focusing on all the possible transcription factors (TFs) in Pseudomonas aeruginosa, enabling comprehensive identification of essential genes and new factors for antibiotic resistance.
2021-08-10 | GSE164797 | GEO
Project description:Site saturation mutagenesis of 500 human protein domains
| PRJNA1105013 | ENA
Project description:Muscarinic acetylcholine receptor M3 (M3) and its downstream effector Gq/11 are critical drug development targets given their involvement in numerous physiological processes and diseases. Although a cryo-electron microscopy study previously defined the structure of the M3-miniGq complex, the lack of information on the intracellular loop 3 (ICL3) of M3 and α-helical domain (AHD) of Gαq has made it difficult to comprehend the molecular mechanism of M3-Gq coupling fully. Here, we present the molecular mechanism underlying the dynamic interactions between the wild-type full-length M3 and heterotrimeric Gq using hydrogen-deuterium exchange mass spectrometry and NanoLuc Binary Technology-based cell systems. This study suggests potential binding interfaces between M3 and Gq in pre-assembled and fully active nucleotide-free complexes. In addition to well-known binding interfaces, we observed the interaction of long ICL3 with Gβγ. Furthermore, M3 ICL3 negatively affected M3-Gq coupling, and the Gαq AHD underwent unique conformational changes during M3-Gq coupling. Therefore, we propose a comprehensive molecular mechanism of M3-Gq coupling by analyzing previously well-defined binding interfaces and neglected regions, such as M3 ICL3 and the Gαq AHD.
2024-05-22 | PXD042562 | Pride
Project description:Encouraged by the dependence of drug-resistant, metastatic cancers on GPX4, we examined biophysical mechanisms of GPX4 inhibition, which revealed an unexpected allosteric binding site. We found that this site was involved in native modulation of GPX4 activity. Binding of inhibitors to this allosteric site caused a conformational change, inhibition of activity, and subsequent cellular GPX4 protein degradation. To verify this binding site in an unbiased manner, we screened a library of compounds, and identified and validated that a novel additional compound can bind in this allosteric site, inhibiting and degrading GPX4. We determined co-crystal structures of six different inhibitors bound in this site. We have thus discovered a new allosteric mechanism for small molecules targeting aggressive cancers dependent on GPX4.
2022-10-12 | MSV000090526 | MassIVE
Project description:The aim of this study was to investigate the function of Laf4 in the brain by focusing on its role in the developing cortex. By manipulating expression levels in organotypic slices, we demonstrate that Laf4 is required for normal cellular migration in the cortex and have subsequently identified Mdga2, an important structural protein in neurodevelopment, as a direct target of Laf4 transcriptional activity.
2014-07-01 | E-MTAB-2520 | biostudies-arrayexpress
Project description:Alternative splicing of pre-mRNA is a prominent mechanism to generate protein diversity, yet its regulation is poorly understood. Here, we demonstrate a direct role for histone modifications in alternative splicing. We find distinctive histone modification signatures which correlate with splicing outcome in a set of human genes. Modulation of histone modifications causes splice site switching. The mechanism for histone-mediated splice site selection involves a histone mark which is read by a chromatin protein, which in turn recruits a splicing regulator. These results outline an adaptor system for reading of histone marks by the pre-mRNA splicing machinery.
2010-02-10 | GSE19373 | GEO
Project description:Site-directed mutagenesis of soybean
| PRJDB10633 | ENA
Project description:Alternative splicing of pre-mRNA is a prominent mechanism to generate protein diversity, yet its regulation is poorly understood. Here, we demonstrate a direct role for histone modifications in alternative splicing. We find distinctive histone modification signatures which correlate with splicing outcome in a set of human genes. Modulation of histone modifications causes splice site switching. The mechanism for histone-mediated splice site selection involves a histone mark which is read by a chromatin protein, which in turn recruits a splicing regulator. These results outline an adaptor system for reading of histone marks by the pre-mRNA splicing machinery. To obtain an estimate of how many PTB-dependent alternative splicing events are regulated by SET2/MRG15-mediated recruitment of PTB, we carried out a genomewide comparative analysis of alternative splicing in hMSC cells depleted of either SETD2, MRG15 or PTB using specific siRNAs, or mock-depleted using a control siRNA.
2010-02-10 | E-GEOD-19373 | biostudies-arrayexpress
Project description:<p>Tick-borne encephalitis virus is an enveloped, pathogenic, RNA virus in the family Flaviviridae, genus Flavivirus. Viral particles are formed when the nucleocapsid, consisting of an RNA genome and multiple copies of the capsid protein, buds through the endoplasmic reticulum membrane and acquires the viral envelope and the associated proteins. The coordination of the nucleocapsid components to the sites of assembly and budding are poorly understood. Here, we investigate nucleocapsid assembly by characterizing the interactions of the wild-type and truncated capsid proteins with membranes by using biophysical methods and model membrane systems. We show that capsid protein initially binds membranes via electrostatic interactions with negatively-charged lipids which is followed by membrane insertion. Additionally, we show that membrane-bound capsid protein can recruit viral genomic RNA. We confirm the biological relevance of the biophysical findings by using mass spectrometry to show that purified virions contain negatively-charged lipids. Our results suggest that nucleocapsid assembly is coordinated by negatively-charged membrane patches on the endoplasmic reticulum and that the capsid protein mediates direct contacts between the nucleocapsid and the membrane.</p>
2023-01-06 | MTBLS6076 | MetaboLights