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      The Hsp70/J-protein machinery of the African trypanosome, Trypanosoma brucei

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          Abstract

          <p class="first" id="Par1">The etiological agent of the neglected tropical disease African trypanosomiasis, <i>Trypanosoma brucei</i>, possesses an expanded and diverse repertoire of heat shock proteins, which have been implicated in cytoprotection, differentiation, as well as progression and transmission of the disease. Hsp70 plays a crucial role in proteostasis, and inhibition of its interactions with co-chaperones is emerging as a potential therapeutic target for numerous diseases. In light of genome annotations and the release of the genome sequence of the human infective subspecies, an updated and current in silico overview of the Hsp70/J-protein machinery in both <i>T. brucei brucei</i> and <i>T. brucei gambiense</i> was conducted. Functional, structural, and evolutionary analyses of the <i>T. brucei</i> Hsp70 and J-protein families were performed. The Hsp70 and J-proteins from humans and selected kinetoplastid parasites were used to assist in identifying proteins from <i>T. brucei</i>, as well as the prediction of potential Hsp70–J-protein partnerships. The Hsp70 and J-proteins were mined from numerous genome-wide proteomics studies, which included different lifecycle stages and subcellular localisations. In this study, 12 putative Hsp70 proteins and 67 putative J-proteins were identified to be encoded on the genomes of both <i>T. brucei</i> subspecies. Interestingly there are 6 type III J-proteins that possess tetratricopeptide repeat-containing (TPR) motifs. Overall, it is envisioned that the results of this study will provide a future context for studying the biology of the African trypanosome and evaluating Hsp70 and J-protein interactions as potential drug targets. </p><div class="section"> <a class="named-anchor" id="d9266081e150"> <!-- named anchor --> </a> <h5 class="section-title" id="d9266081e151">Electronic supplementary material</h5> <p id="d9266081e153">The online version of this article (10.1007/s12192-018-0950-x) contains supplementary material, which is available to authorized users. </p> </div>

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          Genomic sequencing has made it clear that a large fraction of the genes specifying the core biological functions are shared by all eukaryotes. Knowledge of the biological role of such shared proteins in one organism can often be transferred to other organisms. The goal of the Gene Ontology Consortium is to produce a dynamic, controlled vocabulary that can be applied to all eukaryotes even as knowledge of gene and protein roles in cells is accumulating and changing. To this end, three independent ontologies accessible on the World-Wide Web (http://www.geneontology.org) are being constructed: biological process, molecular function and cellular component.
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              Hsp70 chaperones: Cellular functions and molecular mechanism

              Abstract. Hsp70 proteins are central components of the cellular network of molecular chaperones and folding catalysts. They assist a large variety of protein folding processes in the cell by transient association of their substrate binding domain with short hydrophobic peptide segments within their substrate proteins. The substrate binding and release cycle is driven by the switching of Hsp70 between the low-affinity ATP bound state and the high-affinity ADP bound state. Thus, ATP binding and hydrolysis are essential in vitro and in vivo for the chaperone activity of Hsp70 proteins. This ATPase cycle is controlled by co-chaperones of the family of J-domain proteins, which target Hsp70s to their substrates, and by nucleotide exchange factors, which determine the lifetime of the Hsp70-substrate complex. Additional co-chaperones fine-tune this chaperone cycle. For specific tasks the Hsp70 cycle is coupled to the action of other chaperones, such as Hsp90 and Hsp100.
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                Author and article information

                Journal
                Cell Stress and Chaperones
                Cell Stress and Chaperones
                Springer Science and Business Media LLC
                1355-8145
                1466-1268
                January 2019
                December 1 2018
                January 2019
                : 24
                : 1
                : 125-148
                Article
                10.1007/s12192-018-0950-x
                6363631
                30506377
                216b21eb-1cde-4f9e-9d80-a89f44dc1320
                © 2019

                http://www.springer.com/tdm

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