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A variety of autoimmune disorders are associated with an increased risk of thrombosis. Previous studies have suggested combined therapy of heparin and therapeutic plasma exchange (TPE) with fresh frozen plasma (FFP) as the replacement fluid is beneficial in some cases of acute flare-up of autoimmune diseases complicated by thrombotic events. Nevertheless, it remains unknown whether clinicians do more harm than good by exposing patients to a "thrombotic storm" through simultaneous administration of heparin and the clotting factors in the FFP during TPE.
View Article and Find Full Text PDFThe mechanism of discriminative aminoacylation by isoleucyl-tRNA synthetase based on wobble nucleotide recognition.
Nat Commun
December 2024
State Key Laboratory of Anti-Infective Drug Discovery and Development, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
The faithful charging of amino acids to cognate tRNAs by aminoacyl-tRNA synthetases (AARSs) determines the fidelity of protein translation. Isoleucyl-tRNA synthetase (IleRS) distinguishes tRNA from tRNA solely based on the nucleotide at wobble position (N34), and a single substitution at N34 could exchange the aminoacylation specificity between two tRNAs. Here, we report the structural and biochemical mechanism of N34 recognition-based tRNA discrimination by Saccharomyces cerevisiae IleRS (ScIleRS).
View Article and Find Full Text PDFStructural insights into GrpEL1-mediated nucleotide and substrate release of human mitochondrial Hsp70.
Nat Commun
December 2024
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA.
Maintenance of protein homeostasis is necessary for cell viability and depends on a complex network of chaperones and co-chaperones, including the heat-shock protein 70 (Hsp70) system. In human mitochondria, mitochondrial Hsp70 (mortalin) and the nucleotide exchange factor (GrpEL1) work synergistically to stabilize proteins, assemble protein complexes, and facilitate protein import. However, our understanding of the molecular mechanisms guiding these processes is hampered by limited structural information.
View Article and Find Full Text PDFPlasma Exchange and N-Acetylcysteine Therapy in a Case of Congenital Thrombotic Thrombocytopenic Purpura Presenting With Acute Renal Failure.
J Pediatr Hematol Oncol
January 2025
Departments of Pediatric Hematology.
Congenital thrombotic thrombocytopenic purpura (cTTP), which is associated with mutations in the gene for a disintegrin and metalloproteinase with a thrombospondin type 1 motif member 13 (ADAMTS13), is a chronic and lifelong disease. The clinical course is variable. Regularly using ADAMTS13-containing products such as fresh frozen plasma (FFP) for long-term prophylaxis is the most important treatment to prevent thrombotic microangiopathy (TMA) episodes.
View Article and Find Full Text PDFA structure-based analysis of the Kell blood group system.
Front Immunol
December 2024
Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein (UKSH) and Christian-Albrechts-University of Kiel, Kiel, Germany.
Kell is one of the most complex blood group systems, with a highly polymorphic genetic background. Extensive allelic variations in the gene affect the encoded erythrocyte surface protein Kell. Genetic variants causing aberrant splicing, premature termination of protein translation, or specific amino acid exchanges lead to a variety of different phenotypes with altered Kell expression levels or changes in the antigenic properties of the Kell protein.
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