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  • 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

  • Three-dimensional envelope and subunit interactions of the plastid-encoded RNA polymerase from Sinapis alba

    • Authors : Ruedas, Rémi (2023)

  • RNA polymerases (RNAPs) involved in gene transcription are found in all living organisms with degrees of complexity ranging from single polypeptide chains to multimeric enzymes. In the chloroplasts, the nuclear-encoded RNA polymerase and the plastid-encoded RNA polymerase (PEP) are both involved in the selective transcription of the plastid genome. The PEP is a prokaryotic-type multimeric RNAP found in different states depending on light stimuli ...
  • Journal article

  • Ambient temperature crystal structure of Escherichia coli CyaY protein displays alternate conformation

    • Authors : Shafiei, Alaleh (2023)

  • Frataxin is a 23 KDa mitochondrial iron-binding protein that is involved in biogenesis of iron sulfur clusters. A deficiency in frataxin leads to Friedreich's ataxia, a progressive neurodegenerative disorder. The bacterial ortholog of eukaryotic mitochondrial frataxin, CyaY, is thought to play a role in iron sulfur cluster assembly as an iron supplier, making it an important target for study. Here, we present the first ambient tem...
  • Journal article

  • Computational design of Matrix Metalloprotenaise-9 (MMP-9) resistant to auto-cleavage

    • Authors :  Bonadio, Alessandro (2023)

  • Matrix metalloproteinase-9 (MMP-9) is an endopeptidase that remodels the extracellular matrix and has been implicated as a major driver in cancer metastasis. Hence, there is a high demand for MMP-9 inhibitors for therapeutic purposes. For such drug design efforts, large amounts of MMP-9 are required. Yet, the catalytic domain of MMP-9 (MMP-9Cat) is an intrinsically unstable enzyme that tends to auto-cleave within minutes, making it di...
  • Journal Article

  • Evolving spike-protein N-glycosylation in SARS-CoV-2 variants

    • Authors : Baboo, Sabyasachi (2023)

  • It has been three years since SARS-CoV-2 emerged and the world plunged into a “once in a century” pandemic. Since then, multiple waves of infection have swept through the human population, led by variants that were able to evade any acquired immunity. The co-evolution of SARS-CoV-2 variants with human immunity provides an excellent opportunity to study the interaction between viral pathogens and their human hosts. The heavily N-gl...
  • Journal article

  • The cardiac myosin binding protein-C phosphorylation state as a function of multiple protein kinase and phosphatase activities

    • Authors : Kampourakis, Thomas (2023)

  • Phosphorylation of cardiac myosin binding protein-C (cMyBP-C) is a crucial determinant of cardiac myofilament function. Although cMyBP-C phosphorylation by various protein kinases has been extensively studied, the influence of protein phosphatases on cMyBP-C’s multiple phosphorylation sites has remained largely obscure. Here we provide a detailed biochemical characterization of cMyBP-C dephosphorylation by protein phosphatases 1 and 2A (PP1 and PP2A) and deve...
  • Journal article

  • The amino acid composition of a protein influences its expression

    • Authors : Thompson, Reece (2023)

  • The quantity of each protein in a cell only is only partially correlated with its gene transcription rate. Independent influences on protein synthesis levels include mRNA sequence motifs, amino acyl-tRNA synthesis levels, elongation factor action, and protein susceptibility to degradation. Here we report two novel forms of interaction between the amino acid composition of a protein and its expression level. In animals, the differing origin...
  • Journal article

  • A conformational-dependent interdomain redox relay at the core of Protein Disulfide Isomerase activity

    • Authors : Melo, Eduardo P. (2023)

  • Protein disulfide isomerases (PDIs) are a family of molecular chaperones resident in the endoplasmic reticulum (ER) emerging as important factors in disease. In addition to an holdase function, some members catalyse disulfide bond formation and isomerization, a crucial step for native folding and prevention of aggregation of misfolded proteins. PDIs are characterized by a modular arrangement of thioredoxin-like domains, with the canonical, first identified PDIA1, ...
  • 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...