doi:10.1016/j.bbamcr.2020.118727 Abstract The Ser/Thr protein phosphatase Ppz1 from Saccharomyces cerevisiae is the best characterized member of a family of enzymes only found in fungi. Ppz1 is regulated in vivo by two inhibitory subunits, Hal3 and Vhs3, which are moonlighting proteins also involved in the decarboxylation of the 4-phosphopantothenoylcysteine (PPC) intermediate required for coenzyme A biosynthesis. It has been reported that, when overexpressed, Ppz1 is the most toxic protein in yeast. However, the reasons for such toxicity have not been elucidated. Here we show that the detrimental effect of excessive Ppz1 expression is due to an increase in its phosphatase activity and not to a plausible down-titration of the PPC decarboxylase components. We have identified several
/doi/full/10.1080/14756366.2020.1816999 Abstract Parkinson’s disease is one of the most common neurodegenerative disorders in elderly age. One of the mechanisms involved in the neurodegeneration appears related to the aggregation of the presynaptic protein alpha synuclein (α-syn) into toxic oligomers and fibrils. To date, no highly effective treatment is currently available; therefore, there is an increasing interest in the search of new therapeutic tools. The modulation of α-syn aggregation represents an emergent and promising disease-modifying strategy for reducing or blocking the neurodegenerative process. Herein, by combining in silico and in vitro screenings we initially identified 3-(cinnamylsulfanyl)-5-(4-pyridinyl)-1,2,4-triazol-4-amine (3) as α-syn aggregation inhibitor that
https://doi.org/10.1093/dnares/dsaa019 Abstract Transmission Ratio Distortion (TRD), the uneven transmission of an allele from a parent to its offspring, can be caused by allelic differences affecting gametogenesis, fertilization or embryogenesis. However, TRD remains vaguely studied at a genomic scale. We sequenced the diploid and haploid genomes of 3 boars from leukocytes and spermatozoa at 50x to shed light into the genetic basis of spermatogenesis-caused Allelic Ratio Distortion (ARD). We first developed a binomial model to identify ARD by simultaneously analysing all three males. This led to the identification of 55 ARD SNPs, most of which were animal-specific. We then evaluated ARD individually within each pig by a Fisher Exact Test and identified 2 shared genes (TOP3A ...
https://pubs.acs.org/doi/10.1021/acs.biomac.0c01103 Abstract Natural selection has endorsed proteins with amazing structures and functionalities that cannot be matched by synthetic means, explaining the exponential interest in developing protein-based materials. Protein self-assembly allows fabricating complex supramolecular structures from relatively simple building blocks, a bottom-up strategy naturally employed by amyloid fibrils. However, the design of amyloid inspired materials with biological activity is inherently difficult. Here we exploit a modular procedure to generate functional amyloid nanostructures with tight control of their mesoscopic properties. The soft amyloid core of a yeast prion was fused to dihydrofolate reductase through flexible linkers of different s...
Published:August 06, 2020DOI:https://doi.org/10.1016/j.tig.2020.06.008 Highlights The mammalian Y chromosome has been proposed to be a wimp with impending demise should it lose sex-determining function. Changes in sex-determining switches are common in non-mammalian vertebrates, so an alternative explanation is required to explain Y chromosome persistence. The Y chromosome bears executioner genes that are essential for male meiosis, but must themselves also be subjected to meiotic silencing because they are pachytene lethal. The only heritable location that executioner genes can transpose to is the X chromosome (just 5% of the genome), where they remain subject to appropriate meiotic silencing. Transposition of executioner genes away from the Y chromoso...
DOI:https://doi.org/10.1016/j.tibs.2020.08.003 Highlights Divalent cations are essential agents in life with myriads of molecular functions and lesser known structural roles, acting as glue-like agents. By exploiting the architectonic properties of Zn 2+ and others, novel protein materials are generated, including particles, fibers, matrices, and a diversity of ordered and amorphous clusters. These materials result from the controlled coordination of divalent cations, at physiological concentrations, with histidine-rich proteins. Among them, soluble self-assembling oligomers serve as protein-only nanomedicines or nanocarriers for intravenous administration. Amyloidal protein clusters mimic the function of endocrine secretory granules, releasing protein dr
La Agencia Estatal de Investigación publicó recientemente en la sede electrónica del Ministerio de Ciencia e Innovación la resolución de concesión de ayudas a «proyectos de i+d+i» en el marco de los programas estatales de generación de conocimiento y fortalecimiento científico y tecnológico del sistema de i+d+ i y de i+d+ i orientada a los retos de la sociedad, de la convocatoria 2019. Estas ayudas, que permiten fomentar la generación y el avance significativo del conocimiento científico y la investigación de calidad, financiaran un total de 2918 proyectos, seleccionados en régimen de concurrencia competitiva de un total de 6533 presentados. Se ha captado financiación para 7 proyectos científicos liderados por distintos investigadores del IBB, por un importe total que asciende a más d
https://doi.org/10.1007/s11274-020-02875-6 Abstract The resistance of microorganisms to heavy metals in polluted environments is mediated by genetically determined mechanisms. One such mechanism includes the intracellular sequestration of heavy metals in polyphosphate (polyP) inclusions. In Cr(III) contaminated mediums, Ochrobactrum anthropi DE2010 is able to bind and sequester Cr(III) in polyP inclusions. In order to further study the relationship between Cr(III) tolerance and polyP production in O. anthropi DE2010, we carried out whole genomic sequencing, analysis of single nucleotide polymorphisms (SNPs), polyP chemical quantification, and determination of the relative abundance and morphometry of polyP inclusions. In the O. anthropi DE2010 genome, six polyP and pyrophosphate (PPi
Int. J. Mol. Sci. 2020, 21(16), 5814; https://doi.org/10.3390/ijms21165814 Santos, J.; Iglesias, V.; Pintado, C.; Santos-Suárez, J.; Ventura, S. DispHred: A Server to Predict pH-Dependent Order–Disorder Transitions in Intrinsically Disordered Proteins. Int. J. Mol. Sci. 2020, 21, 5814. Abstract The natively unfolded nature of intrinsically disordered proteins (IDPs) relies on several physicochemical principles, of which the balance between a low sequence hydrophobicity and a high net charge appears to be critical. Under this premise, it is well-known that disordered proteins populate a defined region of the charge–hydropathy (C–H) space and that a linear boundary condition is sufficient to distinguish between folded and disordered proteins, an approach widely applied for the
Abstract Growth factors are required for cell proliferation and differentiation under physiological conditions but especially in the context of regenerative medicine. The time-prolonged administration of those factors has been explored using different sustained drug delivery systems. These platforms include natural materials such as bacterial inclusion bodies (IBs) that contain chaperones and other bacterial components that might favour protein release. Being successful from a functional point of view, IBs pose regulatory concerns to clinical applications because of the mentioned presence of bacterial cell components, including endotoxins. We have here explored the release and activity of the human fibroblast growth factor-2 (hFGF-2) from a novel synthetic material