Glucan linked to proteins is a natural mega-glycoconjugate (mGC) playing the central role as a structural component of a yeast cell wall (CW). Regulation of functioning of non-covalently bound glucanosyltransglycosylases (ncGTGs) that have to remodel mGC to provide CW extension is poorly understood. We demonstrate that the main ncGTGs Bgl2 and Scw4 have phosphorylated and glutathionylated residues and are represented in CW as different pools of molecules having various firmness of attachment. Identified pools contain Bgl2 molecules with unmodified peptides, but differ from each other in the presence and combination of modified ones, as well as in the presence or absence of other CW proteins. Correlation of Bgl2 distribution among pools and its N-glycosylation was not found. Glutathione affects Bgl2 conformation, probably resulting in the mode of its attachment and enzymatic activity. Bgl2 from the pool of unmodified and monophosphorylated molecules demonstrates the ability to fibrillate after isolation from CW. Revealing of Bgl2 microcompartments and their mosaic arrangement summarized with the results obtained give the evidence that the functioning of ncGTGs in CW can be controlled by reversible post-translational modifications and facilitated due to their compact localization. The hypothetical scheme of distribution of Bgl2 inside CW is represented.
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http://dx.doi.org/10.3390/ijms21218304 | DOI Listing |
STAR Protoc
January 2025
Department of Chemistry, School of Science, Westlake University, Hangzhou, Zhejiang Province 310030, China; Institute of Natural Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang Province 310024, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang Province 310024, China. Electronic address:
Post-translational modifications (PTMs) of histone H4 play significant roles in the regulation of chromatin status. Here, we present a protocol for semisynthesis of histone H4 by sortase-mediated ligation (SML). We describe steps for solid-phase peptide synthesis of H4R40C(1-42), recombinant expression and purification of H4(41-102), expression and purification of eSrt(2A-9), and preparation of acrylamidine.
View Article and Find Full Text PDFCancer Chemother Pharmacol
January 2025
Clinical Pharmacology and Translational Sciences, Pfizer Worldwide R&D, 10555 Science Center Drive, San Diego, CA, 92121, USA.
As development of new oncology small molecule therapies is focused mainly on molecularly targeted agents, the dose selection paradigm has shifted from the maximum tolerated dose (MTD)-based approach traditionally utilized with cytotoxic drugs towards determining an optimal dose with long-term tolerability while maintaining efficacy. To assess overall tolerability in recently approved oncology small molecules, we surveyed 54 compounds approved by the FDA since March 2017 with respect to dose intensity, dose modifications, and treatment emergent adverse events (TEAEs). Of the 54 new molecular entities surveyed, only 15 were approved at a label dose equal to the MTD (Label Dose = MTD).
View Article and Find Full Text PDFAnal Chem
January 2025
Molecular and Cellular Biology Graduate Program, University of Massachusetts, Amherst, Massachusetts 01003, United States.
Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) has been used to generate spatial maps of lipids, metabolites, peptides, proteins, and glycans in tissues; however, its use for mapping extracellular matrix (ECM) protein distributions is underexplored. ECM proteins play a major role in various pathological conditions, and changes in their spatial distributions affect the function and morphology of cells within tissues. ECM protein detection is challenging because they are large, insoluble, and undergo various post-translational modifications, such as glycosylation.
View Article and Find Full Text PDFVet Immunol Immunopathol
December 2024
Department of Biochemistry, Bahauddin Zakariya University, Multan 66000, Pakistan. Electronic address:
The Hendra virus (HeV) has resulted in epidemics of respiratory and neurological illnesses in animals. Humans have contracted diseases with high fatality rates as a result of infected domestic animals, but effective vaccinations and therapies are currently not available against HeV. Herein, we analyzed the proteome of HeV and constructed an effective and innovative multi-epitope vaccine using immunoinformatics techniques.
View Article and Find Full Text PDFArch Immunol Ther Exp (Warsz)
January 2025
Department of Human Physiology, Medical University of Lublin, Lublin, Poland.
Systemic lupus erythematosus (SLE) is an autoimmune disease whose pathogenesis is not fully understood to date. One of the suggested mechanisms for its development is NETosis, which involves the release of a specific network consisting of chromatin, proteins, and enzymes from neutrophils, stimulating the immune system. One of its markers is citrullinated histone H3 (H3Cit).
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