Unveiling potential inhibitors targeting the nucleocapsid protein of SARS-CoV-2: Structural insights into their binding sites.

The Nucleocapsid (N) protein of SARS-CoV-2 plays a crucial role in viral replication and pathogenesis, making it an attractive target for developing antiviral therapeutics. In this study, we used differential scanning fluorimetry to establish a high-throughput screening method for identifying high-affinity ligands of N-terminal domain of the N protein (N-NTD). We screened an FDA-approved drug library of 1813 compounds and identified 102 compounds interacting with N-NTD.

Backbone triple resonance assignments of the dimerization domain of NF-kappaB p52 subunit.

NF-kappaB is a family of inducible transcription factors playing an important role in immune response in vertebrates. All the five members of the family function as dimers in various combinations. Though all the family members recognize and bind to similar DNA elements to regulate the transcription of its target genes, the dimer composition can lead to differential transcriptional outcomes.

Expression, Purification, and Refolding of Chikungunya Virus Full-Length Envelope E2 Protein along with B-Cell and T-Cell Epitope Analyses Using Immuno-Informatics Approaches.

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus, which causes severe illness in humans and is responsible for epidemic outbreaks in Africa, Asia, North and South America, and Europe. Despite its increased global prevalence, no licensed vaccines are available to date for treating or preventing CHIKV infection. The envelope E2 protein is one of the promising subunit vaccine candidates against CHIKV.

Insights into the NF-κB-DNA Interaction through NMR Spectroscopy.

Transcription factors bind specifically to their target elements in the genome, eliciting specific gene expression programs. The nuclear factor-κB (NF-κB) system is a family of proteins comprising inducible transcription activators, which play a critical role in inflammation and cancer. The NF-κB members function as dimers with each monomeric unit binding the κB-DNA.

Domain Stability Regulated through the Dimer Interface Controls the Formation Kinetics of a Specific NF-κB Dimer.

The NF-κB family of transcription factors is a key regulator of the immune response in the vertebrates. The family comprises five proteins that function as dimers formed in various combinations among the members, with the RelA-p50 dimer being physiologically the most abundant. While most of the 15 possible dimers are scarcely present in the cell with some remaining experimentally undetected to date, there are specific gene sets that are only activated by certain sparsely populated NF-κB dimers.

Backbone resonance assignments of the dimeric domain of the p50 NF-kappaB subunit.

The Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) is a family of transcription factor recognizing a 9-11 base pair kappaB sites on the promoter/enhancer region of their target genes. The family comprises of five members forming dimers amongst themselves in various combinations. Here we report the backbone resonance assignments of the 24 kDa homodimer of the p50 subunit of NF-kappaB.

Super-Resolved Nuclear Magnetic Resonance Spectroscopy.

We present a novel method that breaks the resolution barrier in nuclear magnetic resonance (NMR) spectroscopy, allowing one to accurately estimate the chemical shift values of highly overlapping or broadened peaks. This problem is routinely encountered in NMR when peaks have large linewidths due to rapidly decaying signals, hindering its application. We address this problem based on the notion of finite-rate-of-innovation (FRI) sampling, which is based on the premise that signals such as the NMR signal, can be accurately reconstructed using fewer measurements than that required by existing approaches.

Structural characterization of the ternary complex that mediates termination of NF-κB signaling by IκBα.

The transcription factor NF-κB is used in many systems for the transduction of extracellular signals into the expression of signal-responsive genes. Published structural data explain the activation of NF-κB through degradation of its dedicated inhibitor IκBα, but the mechanism by which NF-κB-mediated signaling is turned off by its removal from the DNA in the presence of newly synthesized IκBα (termed stripping) is unknown. Previous kinetic studies showed that IκBα accelerates NF-κB dissociation from DNA, and a transient ternary complex between NF-κB, its cognate DNA sequence, and IκBα was observed.

NMR characterization of a 72 kDa transcription factor using differential isotopic labeling.

NF-κB is a major transcription factor that mediates a number of cellular signaling pathways. Crystal structure analysis gives an incomplete picture of the behavior of the protein, particularly in the free state; free monomers or dimers of NF-κB have never been crystallized. NMR analysis gives insights into the structure and dynamics of the protein in solution, but a necessary first step is the assignment of resonances.

Analysis of the RelA:CBP/p300 interaction reveals its involvement in NF-κB-driven transcription.

NF-κB plays a vital role in cellular immune and inflammatory response, survival, and proliferation by regulating the transcription of various genes involved in these processes. To activate transcription, RelA (a prominent NF-κB family member) interacts with transcriptional co-activators like CREB-binding protein (CBP) and its paralog p300 in addition to its cognate κB sites on the promoter/enhancer regions of DNA. The RelA:CBP/p300 complex is comprised of two components--first, DNA binding domain of RelA interacts with the KIX domain of CBP/p300, and second, the transcriptional activation domain (TAD) of RelA binds to the TAZ1 domain of CBP/p300.