Tìm kiếm nâng cao

Current filters:
Current filters:

Discover

Search Results

Item hits:
  • Journal Article

  • Structural properties of the HNF-1A transactivation domain

    • Authors : Kind, Laura (2023)

  • Hepatocyte nuclear factor 1α (HNF-1A) is a transcription factor with important gene regulatory roles in pancreatic β-cells. HNF1A gene variants are associated with a monogenic form of diabetes (HNF1A-MODY) or an increased risk for type 2 diabetes. While several pancreatic target genes of HNF-1A have been described, a lack of knowledge regarding the structure-function relationships in HNF-1A prohibits a detailed understanding of HNF-1A-mediated gene transcription, ...
  • Journal Article

  • Thiaproline accelerates the slow folding phase of proteins containing cis prolines in the native state by two orders of magnitude

    • Authors : Loughlin, Jennie O’ (2023)

  • The cis/trans isomerization of peptidyl-prolyl peptide bonds is often the bottleneck of the refolding reaction for proteins containing cis proline residues in the native state. Proline (Pro) analogues, especially C4-substituted fluoroprolines, have been widely used in protein engineering to enhance the thermodynamic stability of peptides and proteins and to investigate folding kinetics. 4-thiaproline (Thp) has been shown to bias the ring pucker of Pro, to inc...
  • Journal Article

  • Type III-B CRISPR-Cas signaling-based cascade of proteolytic cleavages

    • Authors : Steens, Jurre A. (2023)

  • Type III CRISPR-Cas systems provide a sequence-specific adaptive immune response that protects prokaryotic hosts against viruses and other foreign genetic invaders. These crRNA-guided Cas effector complexes bind and cleave complementary RNA targets. Specific target binding stimulates the Cas10 subunit to generate cyclic oligoadenylate (cOA) signaling molecules, that in turn allosterically activate proteins carrying cognate sensory domains: CARF or SAVED. Here, we characterize an...
  • Journal Article

  • SARS-COV-2 Spike Protein Fragment eases Amyloidogenesis of α-Synuclein

    • Authors : Chesney, Andrew D (2023)

  • Parkinson’s Disease is accompanied by presence of amyloids in the brain formed of α-synuclein chains. Correlation between COVID-19 and the onset of Parkinson’s disease let to the idea that amyloidogenic segments in SARS-COV-2 proteins can induce aggregation of α-synuclein. Using molecular dynamic simulations, we show that the fragment FKNIDGYFKI of the spike protein, which is unique for SARS-COV-2, shifts preferentially the ensemble of α-synuclein&#x...
  • Journal article

  • Coenzyme A binding sites induce proximal acylation across protein families

    • Authors : Carrico, Chris (2023)

  • Lysine Nɛ-acylations, such as acetylation or succinylation, are post-translational modifications that regulate protein function. In mitochondria, lysine acylation is predominantly non-enzymatic, and only a specific subset of the proteome is acylated. Coenzyme A (CoA) can act as an acyl group carrier via a thioester bond, but what controls the acylation of mitochondrial lysines remains poorly understood. Using published datasets, here we found that pr...
  • Journal article

  • Lipid nanodiscs as a template for high-resolution cryo-EM structures of peripheral membrane proteins

    • Authors : Cannon, Kevin S. (2023)

  • processes such as signal transduction, membrane trafficking, and autophagy. Transient binding to the membrane has a profound impact on protein function, serving to induce conformational changes and alter biochemical and biophysical parameters by increasing the local concentration of factors and restricting diffusion to two dimensions. Despite the centrality of the membrane in serving as a template for cell biology, there are few reported highresolution stru...
  • Journal article

  • Chemoproteomics-Enabled Discovery of a Covalent Molecular Glue Degrader Targeting NF-κB

    • Authors : King, Elizabeth A. (2023)

  • Targeted protein degradation using heterobifunctional Proteolysis-Targeting Chimeras (PROTACs) or molecular glues has arisen as a powerful therapeutic modality for degrading disease targets. While PROTAC design is becoming more modular and straightforward, the discovery of novel molecular glue degraders has been more challenging. While several recent studies have showcased phenotypic screening and counter-screening approaches to discover new molecular glue degraders, me...
  • Journal article

  • A database of accurate electrophoretic migration patterns for human proteins in cell lines

    • Authors : Mylonas, Roman (2023)

  • Native molecular weight (MW) is one of the defining features of proteins. Denaturing gel electrophoresis (SDS-PAGE) is a very popular technique for separating proteins and determining their MW. Coupled with antibody-based detection, SDS-PAGE is widely applied for protein identification and quantitation. Yet, electrophoresis is poorly reproducible and the MWs obtained are often inaccurate. This hampers antibody validation and negatively impacts the reliability of western...