- Industry article
Authors : Alejandre, Alba Méndez (2023) - Phagosome acidification and proteolysis are essential processes in the immune
response to contain and eliminate pathogens. In recent years, there has been an
increased desire for a rapid and accurate method of assessing these processes in
real-time. Here, we outline the development of a multiplexed assay that allows
simultaneous monitoring of phagosome acidification and proteolysis in the same
sample using silica beads conjugated to pHrodo...
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- Journal article
Authors : Ten, Tensho (2021) - Mint3 is known to enhance aerobic ATP production, known as the Warburg effect, by binding to FIH-1. Since this effect is considered to be beneficial for cancer cells, the interaction is a promising target for cancer therapy. However, previous research has suggested that the interacting region of Mint3 with FIH-1 is intrinsically disordered, which makes investigation of this interaction challenging. Therefore, we adopted a physicochemical approach that co...
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- Journal article
Authors : Ciulla, Daniel A (2023) - The Sonic hedgehog (SHh) precursor protein undergoes biosynthetic autoprocessing to cleave off and cholesterylate the SHh signaling ligand, a vital morphogen and oncogenic effector protein. Autoprocessing is self-catalyzed by SHhC, the SHh precursor’s enzymatic domain. Here we describe the development and validation of the first cellular reporter to monitor human SHhC autoprocessing non-invasively in high-throughput compatible plates. The assay couples intracellular SHhC autopro...
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- Journal Article
Authors : Reddy, Panga Jaipal. (2023) - Lyme disease , caused by an infection with the spirochete Borrelia burgdorferi, is the most common 36 vector-borne disease in North America. B. burgdorferi strains harbor extensive genomic and 37 proteomic variability and further comparison is key to understanding the spirochetes infectivity and 38 biological impacts of identified sequence variants. To achieve this goal, both transcript and mass 39 spectrometry (MS)-based proteomics was applied to assemble pe...
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- Journal article
Authors : Makarov, Dmytro (2023) - Tubulin detyrosination-tyrosination cycle regulates the stability of microtubules. Thus far described on α-tubulins, the tyrosination level is maintained by a single tubulin-tyrosine ligase (TTL). However, the precise dynamics and tubulin isoforms which undergo (de)tyrosination in neurons are unknown. Here, we exploit the substrate promiscuity of the TTL to introduce an O-propargyl-L-tyrosine in neuroblastoma cells and neurons. Mass spectrometry-based chemical proteomics in neuroblas...
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- Journal article
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...
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- Journal article
Authors : Nielsen, Jakob Toudahl (2021) - NMR chemical shifts (CSs) are delicate reporters of local protein structure, and recent advances in
random coil CS (RCCS) prediction and interpretation now offer the compelling prospect of inferring
small populations of structure from small deviations from RCCSs. Here, we present CheSPI, a simple
and efficient method that provides unbiased and sensitive aggregate measures of local structure
and disorder. It is demonstrated that CheSPI can p...
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- Journal article
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...
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- Journal article
Authors : Barik, Sushanta Kumar (2021) - Purification of proteins from human plasma is a herculean task to perform 2-D gel
electrophoresis. Human plasma contains nearly 70% albumin and globulin. The removal of
such high abundance high molecular weight proteins is very difficult before performing 2-D
gel electrophoresis. It becomes more difficult when we intent to investigate in infectious
diseases like HIV/AIDS. We tried to the best of our efforts adopting various organic...
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- Journal article
Authors : Almasy, Katherine M. (2021) - Human coronaviruses have become an increasing threat to global health; three highly pathogenic strains have emerged since the early 2000s, including most recently SARS-CoV-2, the cause of COVID-19. A better understanding of the molecular mechanisms of coronavirus pathogenesis is needed, including how these highly virulent strains differ from those that cause milder, common-cold like disease. While significant progress has been made in understanding how SARS-CoV-2 ...
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- Journal article
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...
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- Journal article
Authors : Henning, Nathaniel J. (2021) - Targeted protein degradation is a powerful therapeutic modality that uses heterobifunctional small-molecules to
induce proximity between E3 ubiquitin ligases and target proteins to ubiquitinate and degrade specific proteins
of interest. However, many proteins are ubiquitinated and degraded to drive disease pathology; in these cases
targeted protein stabilization (TPS), rather than degradation, of the actively degraded target using a smallmolecule
would be ther...
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- Journal article
Authors : Trainor, Brandon M. (2021) - The conventional view regarding regulation of gene expression is based on transcription control.
However, a growing number of recent studies has revealed the important additional impact of
translational regulation. Eukaryotic translational machinery appears to be capable of
reprogramming mRNA translation to generate proteins required to maintain a healthy cellular
proteostasis under particular physiological conditions or to adapt to stress. Altho...
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- Journal Article
Authors : Muir, Tom W. (2023) - The post-translational regulation of protein function is involved in most cellular processes.
As such, synthetic biology tools that operate at this level provide opportunities for manipulating
cellular states. Here, we deploy a proximity-triggered protein trans-splicing technology to enable
the time-resolved synthesis of target proteins from pre-made parts. The modularity of the strategy
allows for the addition or removal of various control elements as&#x...
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- Journal Article
Authors : Ashok, Yashwanth (2023) - The DNA damage response involves a complex protein network with members mediating different post-translational modifications such as ubiquitination and deubiquitination. Thereby the E3 ubiquitin ligase DTX3L as well as the deubiquitinase USP28 are recruited especially to DNA double strand breaks (DSBs) suggesting mutual functional interactions. Here we present evidence for the existence of such crosstalk. Mechanistically we show that DTX3L interacts with USP28 and ubiq...
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- Ebooks (Sách điện tử)
Authors : Karaś, Piotr (2023) - Evolution can tinker with multi-protein machines and replace them with simpler single-protein systems performing equivalent functions in equally efficient manner. It is unclear how, on a molecular level, such simplification can arise. With ancestral reconstruction and biochemical analysis we have traced the evolution of bacterial small heat shock proteins (sHsp), which help to refold proteins from aggregates using either two proteins with different functions (IbpA ...
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- Journal Article
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...
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- Journal Article
Authors : Baboo, Sabyasachi (2023) - UBR4 is an E3 ligase (E3) of the N-degron pathway and is involved in
neurodevelopment, age-associated muscular atrophy and cancer progression. The location
and mechanistic classification of the E3 module within the 600 kDa protein UBR4 remains
unknown. Herein, we identify and characterize, at a biochemical and structural level, a distinct
E3 module within human UBR4 consisting of a novel “hemiRING” zinc finger, a helical-rich
UBR ...
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- Journal Article
Authors : Mendes, Luis Felipe S.; Costa-Filho, Antonio J. (2023) - Eukaryotic cells evolved to possess efficient secretory machinery capable of transporting a significant fraction of their proteome. The number of proteins predicted to enter the secretory pathway can reach up to 36% of the total proteome in humans (1). Proteins entering the secretory pathway are efficiently sorted to a specific destination: the extracellular space, the plasma membrane, or the interior of the endomembrane system. The machinery also has&#x...
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- Journal article
Authors : Ball, Eric H. (2023) - AbstractF
ilter paper provides an excellent matrix for retention of proteins containing a cellulose binding
domain. To use this capability for manipulating recombinant fusion proteins, binding and elution
parameters were explored and procedures developed for small scale purification, modification and
assay. Proteins were tagged with the cellulose binding domain from the C thermocellum CipB gene via
a cleavable linker. Filter paper disks of 6mm&...
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