- Journal Article
Authors : Davies, Jonathan P. (2023) - Coronaviruses (CoV), including SARS-CoV-2, modulate host proteostasis through
activation of stress-responsive signaling pathways such as the Unfolded Protein Response
(UPR), which remedies misfolded protein accumulation by attenuating translation and
increasing protein folding capacity. While CoV nonstructural proteins (nsps) are essential for
infection, little is known about the role of nsps in modulating the UPR. We characterized the
impact of SARS-CoV-2 ns...
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- Journal Article
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...
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- Journal article
Authors : Kotani, Norihiro (2023) - Coronavirus disease (COVID-19) represents a real threat to the global population, and understanding the
biological features of the causative virus, i.e., severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is imperative for mitigating this threat. Analyses of proteins such as primary receptors and co-receptors (co-factors), which are involved in the entry of SARSCoV- 2 into host cells, will provide important clues to help control the virus. Here,&#...
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- Journal article
Authors : Buscagan, Trixia M. (2023) - The nitrogenase Fe protein mediates ATP-dependent electron transfer to the nitrogenase MoFe
protein during nitrogen fixation, in addition to catalyzing MoFe protein independent substrate
(CO2) reduction and facilitating MoFe protein metallocluster biosynthesis. The precise role(s) of
the Fe protein Fe4S4 cluster in some of these processes remains ill-defined. Herein, we report
crystallographic data demonstrating ATP-dependent chalcogenide exchange at the Fe4S4 clus...
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- Journal article
Authors : Noort, Marco van den (2021) - Our understanding of what determines ligand affinity of proteins is poor, even with highresolution structures available. Both the non-covalent ligand-protein interactions and the
relative free energies of available conformations contribute to the affinity of a protein for a
ligand. Distant, non-binding site residues can influence the ligand affinity by altering the free
energy difference between a ligand-free and ligand-bound conformation. Our hypothesis isthat...
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- Journal article
Authors : Chafiaa, Bouguechtouli (2023) - The combined expression of a handful of pluripotency transcription factors (PluriTFs) in
24 somatic cells can generate induced pluripotent stem cells (iPSCs). Here, we report the
25 structural characterization of disordered regions contained in four important PluriTFs, namely
26 Oct4, Sox2, Nanog and Esrrb. Moreover, many post-translational modifications (PTMs) have
27 been detected on PluriTFs, whose roles are not yet characterized. To help in ...
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- Journal article
Authors : Fürsch, Julius (2021) - Small heat-shock proteins (sHSP) are important members of the cellular stress response
in all species. Their best described function is the binding of early unfolding states and
the resulting prevention of protein aggregation. Most sHSPs exist as oligomers but vary
in size and subunit organization. Many sHSPs exist as a polydisperse composition of
oligomers which undergoes changes in subunit composition, folding status and rel...
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- Journal Article
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, ...
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- Journal Article
Authors : chechik, Maria (2023) - The large group of dsDNA viruses comprising tailed bacteriophages and herpesviruses assemble by
packaging their DNA into preformed procapsids. The key component ensuring specific recognition of
bacteriophage DNA from the mixture of all the nucleic acids contained in the host cell, and initiating
its packaging is the small terminase protein. The nascent genome is usually produced as multiple copies, joined head-to-tail, in long concatemers of dsDN...
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- Journal article
Authors : Birke, Ramona (2021) - Sulfonated rhodamines that endow xanthene dyes with cellular impermeability are presented. We
fuse charged sulfonates to red and far-red dyes to obtain Sulfo549 and Sulfo646, respectively, and
further link these to SNAP- and Halo-tag substrates for protein self-labelling. Cellular
impermeability is validated in live cell imaging experiments in transfected HEK cells and neurons
derived from induced pluripotent stem cells (iPSCs). Lastly, we show that&...
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- Journal article
Authors : Stewart, Valley (2023) - Tyrosine sulfation, a post-translational modification, can enhance and often determine
protein-protein interaction specificity. Sulfotyrosyl residues (sTyr) are formed by tyrosylprotein
sulfotransferase during maturation in the golgi apparatus, and most often occur
singly or as a cluster of two or three sTyr within a six-residue span. With both negative
charge and aromatic character, sTyr enables numerous atomic contacts as visualized in
binding interfac...
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- Journal article
Authors : Sabatier, Pierre (2023) - Most drugs used in the clinic and drug candidates target multiple proteins, and thus detailed characterization of their efficacy targets is required. While current methods rely on quantitative measurements at thermodynamic equilibrium, kinetic parameters such as the residence time of a drug on its target provide a better proxy for efficacy in vivo. Here, we present Residence Time Proteome Integral Solubility Alteration (ResT-PISA) assay which provides monitor...
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- Journal article
Authors : Stoeber, Jonathan (2021) - α-Synuclein (αS) is an intrinsically disordered protein (IDP) that aggregates into amyloid fibrils
during the progression of Parkinson’s Disease and other synucleinopathies. The N-terminal
domain (residues 1-60) is now understood to play a critical role in the initial nucleation of
aggregation, as well as a pivotal role in the monomer-fibril interaction underlying amyloid seeding.
Here we report on the interaction between αS and&#x...
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- Journal article
Authors : Dhenin, Jonathan (2021) - Top-down proteomics (TDP) is a powerful technology allowing the char acterization of proteins at the proteoform level using high-resolution tan dem mass spectrometry (MS/MS). Proteoforms correspond to the different
forms of a protein arising from all combinatorial sources of variation from
a single gene (including combinations of genetic variation, alternative
splicing, and post-translational modifications)(Smith and Kelleher, 2018).
The complete...
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- Journal article
Authors : Borvinskaya, Ekaterina V. (2021) - The protein composition (proteome) of cestode Schistocephalus solidus was measured in an experiment simulating the transition of the parasite from a cold-blooded to a warm-blooded host. Infective S. solidus plerocercoids obtained from the three-spined stickleback Gasterosteus aculeatus were heated at 40 °C for 1 hour or cultured in vitro at 40 °C and 22 °C for 48 hours. In the short-term experiment, the content of only one tegument prote...
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- Journal article
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...
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- Journal article
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...
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- Journal article
Authors : LaFrance, Benjamin (2021) - Bacterial nanocompartments, also known as encapsulins, are an emerging class of
protein-based ‘organelles’ found in bacteria and archaea. Encapsulins are virus-like
icosahedral particles comprising a ~25-50 nm shell surrounding a specific cargo
enzyme. Compartmentalization is thought to create a unique chemical environment to
facilitate catalysis and isolate toxic intermediates. Many questions regarding
nanocompartment structure-function remain unanswered, including how...
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- Journal article
Authors : Sennett, Michael A. (2023) - Ancestral sequence resurrection (ASR) is the inference of extinct biological sequences from extant sequences, the most popular of which are based on probabilistic models of evolution. ASR is becoming a popular method for studying the evolution of enzyme characteristics. The properties of ancestral enzymes are biochemically and biophysically characterized to gain some knowledge regarding the origin of some enzyme property. Current methodology relies on resurrection ...
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- Journal article
Authors : Knoke, Lisa R. (2023) - The thiol redox balance in the periplasm of E. coli depends on the DsbA/B pair for oxidative
14 power and the DsbC/D system as its complement for isomerization of non-native disulfides.
15 While the standard redox potentials of those systems are known, the in vivo redox potential
16 imposed onto protein thiol disulfide pairs in the periplasm remains unknown. Here, we used
17 genetically encoded redox probes (roGFP2 ...
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