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Cold Spring Harbor Perspectives in... Sep 2014Four-way DNA intermediates, called Holliday junctions (HJs), can form during meiotic and mitotic recombination, and their removal is crucial for chromosome segregation.... (Review)
Review
Four-way DNA intermediates, called Holliday junctions (HJs), can form during meiotic and mitotic recombination, and their removal is crucial for chromosome segregation. A group of ubiquitous and highly specialized structure-selective endonucleases catalyze the cleavage of HJs into two disconnected DNA duplexes in a reaction called HJ resolution. These enzymes, called HJ resolvases, have been identified in bacteria and their bacteriophages, archaea, and eukaryotes. In this review, we discuss fundamental aspects of the HJ structure and their interaction with junction-resolving enzymes. This is followed by a brief discussion of the eubacterial RuvABC enzymes, which provide the paradigm for HJ resolvases in other organisms. Finally, we review the biochemical and structural properties of some well-characterized resolvases from archaea, bacteriophage, and eukaryotes.
Topics: Archaea; Bacteria; Bacteriophages; Cell Nucleus; DNA Repair; DNA, Cruciform; DNA-Binding Proteins; Endodeoxyribonucleases; Endonucleases; Holliday Junction Resolvases; Humans; Molecular Conformation; Protein Multimerization; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Schizosaccharomyces pombe Proteins
PubMed: 25183833
DOI: 10.1101/cshperspect.a023192 -
Journal of Thrombosis and Haemostasis :... Nov 2020Protein S is a critical regulator of coagulation that functions as a cofactor for the activated protein C (APC) and tissue factor pathway inhibitor (TFPI) pathways. It... (Review)
Review
Protein S is a critical regulator of coagulation that functions as a cofactor for the activated protein C (APC) and tissue factor pathway inhibitor (TFPI) pathways. It also has direct anticoagulant functions, inhibiting the intrinsic tenase and prothrombinase complexes. Through these functions, protein S regulates coagulation during both its initiation and its propagation phases. The importance of protein S in hemostatic regulation is apparent from the strong association between protein S deficiencies and increased risk for venous thrombosis. This is most likely because both APC and TFPIα are inefficient anticoagulants in the absence of any cofactors. The detailed molecular mechanisms involved in protein S cofactor functions remain to be fully clarified. However, recent advances in the field have greatly improved our understanding of these functions. Evidence suggests that protein S anticoagulant properties often depend on the presence of synergistic cofactors and the formation of multicomponent complexes on negatively charged phospholipid surfaces. Their high affinity binding to negatively charged phospholipids helps bring the anticoagulant proteins to the membranes, resulting in efficient and targeted regulation of coagulation. In this review, we provide an update on protein S and how it functions as a critical hemostatic regulator.
Topics: Anticoagulants; Blood Coagulation; Humans; Protein Binding; Protein S; Protein S Deficiency
PubMed: 32702208
DOI: 10.1111/jth.15025 -
Life (Basel, Switzerland) Jul 2021Abnormal and excessive nitrosative stress contributes to neurodegenerative disease associated with the production of pathological levels of misfolded proteins. The... (Review)
Review
Abnormal and excessive nitrosative stress contributes to neurodegenerative disease associated with the production of pathological levels of misfolded proteins. The accumulated findings strongly suggest that excessive NO production can induce and deepen these pathological processes, particularly by the S-nitrosylation of target proteins. Therefore, the relationship between S-nitrosylated proteins and the accumulation of misfolded proteins was reviewed. We particularly focused on the S-nitrosylation of E3-ubiquitin-protein ligase, parkin, and endoplasmic reticulum chaperone, PDI, which contribute to the accumulation of misfolded proteins. In addition to the target proteins being S-nitrosylated, NOS, which produces NO, and GSNOR, which inhibits S-nitrosylation, were also suggested as potential therapeutic targets for protein misfolding-associated diseases.
PubMed: 34357077
DOI: 10.3390/life11070705 -
Molecules (Basel, Switzerland) Aug 2017Protein -sulfhydration is a newly discovered post-translational modification of specific cysteine residue(s) in target proteins, which is involved in a broad range of... (Review)
Review
Protein -sulfhydration is a newly discovered post-translational modification of specific cysteine residue(s) in target proteins, which is involved in a broad range of cellular functions and metabolic pathways. By changing local conformation and the final activity of target proteins, -sulfhydration is believed to mediate most cellular responses initiated by H₂S, a novel gasotransmitter. In comparison to protein -sulfhydration, nitric oxide-mediated protein -nitrosylation has been extensively investigated, including its formation, regulation, transfer and metabolism. Although the investigation on the regulatory mechanisms associated with protein -sulfhydration is still in its infancy, accumulated evidence suggested that protein -sulfhydration may share similar chemical features with protein -nitrosylation. Glutathione persulfide acts as a major donor for protein -sulfhydration. Here, we review the present knowledge on protein -sulfhydration, and also predict its formation and regulation mechanisms based on the knowledge from protein -nitrosylation.
Topics: Animals; Cysteine; Disulfides; Glutathione; Humans; Hydrogen Sulfide; Nitric Oxide; Protein Conformation; Protein Processing, Post-Translational; Proteins
PubMed: 28800080
DOI: 10.3390/molecules22081334 -
Frontiers in Plant Science 2022Protein S-acylation, also known as palmitoylation, is an important lipid post-translational modification of proteins in eukaryotes. S-acylation plays critical roles in a... (Review)
Review
Protein S-acylation, also known as palmitoylation, is an important lipid post-translational modification of proteins in eukaryotes. S-acylation plays critical roles in a variety of protein functions involved in plant development and responses to abiotic and biotic stresses. The status of S-acylation on proteins is dynamic and reversible, which is catalyzed by protein S-acyltransferases (PATs) and reversed by acyl protein thioesterases. The cycle of S-acylation and de-S-acylation provides a molecular mechanism for membrane-associated proteins to undergo cycling and trafficking between different cell compartments and thus works as a switch to initiate or terminate particular signaling transductions on the membrane surface. In plants, thousands of proteins have been identified to be S-acylated through proteomics. Many S-acylated proteins and quite a few PAT-substrate pairs have been functionally characterized. A recently characterized acyl protein thioesterases family, ABAPT family proteins in , has provided new insights into the de-S-acylation process. However, our understanding of the regulatory mechanisms controlling the S-acylation and de-S-acylation process is surprisingly incomplete. In this review, we discuss how protein S-acylation level is regulated with the focus on catalyzing enzymes in plants. We also propose the challenges and potential developments for the understanding of the regulatory mechanisms controlling protein S-acylation in plants.
PubMed: 35968095
DOI: 10.3389/fpls.2022.956231 -
Journal of Medicine and Life Nov 2022This study was conducted to assess the level of proteins C and S in patients with thalassemia intermedia from the Thalassemia Center in Erbil, Iraq. This study aimed to...
This study was conducted to assess the level of proteins C and S in patients with thalassemia intermedia from the Thalassemia Center in Erbil, Iraq. This study aimed to evaluate protein C and S levels in patients with β-thalassemia intermedia and correlate them to different clinical and laboratory parameters. This comprehensive descriptive case-control study was conducted in 2021. Twenty-three thalassemia intermedia patients were recruited. After the participants' demographic data were recorded, plasma levels of both proteins were measured. The acquired files were examined for the 23 patients studied, 48% of whom were female. The mean age of the patients was 16.32 years. The findings show that the proportion of protein C in males was greater than in females, while this percentage contrasts when compared with protein S (ranging between 89-99% and 85-96%, respectively). Concerning age, these two types of protein in children have more value compared to older ages. Only seven people had less than 1,000 ferritins, while the others had higher values. A decrease in proteins C and S was observed in the thalassemia intermediate compared to the control group. There was a significant relationship between the decreased protein C and S levels with splenectomy. Given the significant reduction in protein C and S levels among patients with thalassemia intermediate compared to the control group, there is an increased risk of thromboembolic events in patients with thalassemia intermediate.
Topics: Adolescent; Child; Female; Humans; Male; beta-Thalassemia; Case-Control Studies; Ferritins; Protein C; Protein S; Thromboembolism
PubMed: 36567848
DOI: 10.25122/jml-2021-0316 -
British Journal of Pharmacology Feb 2020Hydrogen sulfide (H S) is a signalling molecule that regulates neuronal transmission, vascular tone, cytoprotection, inflammatory responses, angiogenesis, and oxygen... (Review)
Review
Hydrogen sulfide (H S) is a signalling molecule that regulates neuronal transmission, vascular tone, cytoprotection, inflammatory responses, angiogenesis, and oxygen sensing. Some of these functions have recently been ascribed to its oxidized form polysulfides (H S ), which can be produced by 3-mercaptopyruvate sulfurtransferase (MPST), also known as a H S-producing enzyme. H S activate ion channels, tumour suppressors, transcription factors, and protein kinases. H S S-sulfurate (S-sulfhydrate) cysteine residues of these target proteins to modify their activity by inducing conformational changes through the formation of a disulfide bridge between the two cysteine residues involved. The chemical interaction between H S and NO also generates H S , which may be a chemical entity that exerts the synergistic effect of H S and NO. MPST also produces redox regulators cysteine persulfide (CysSSH), GSH persulfide (GSSH), and persulfurated proteins. In addition to MPST, haemoproteins such as haemoglobin, myoglobin, neuroglobin, and catalase as well as SOD can produce H S , and sulfide quinone oxidoreductase and cysteinyl tRNA synthetase can make GSSH and CysSSH. This review focuses on the recent progress in the study of the production and physiological roles of these persulfurated and polysulfurated molecules. LINKED ARTICLES: This article is part of a themed section on Hydrogen Sulfide in Biology & Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.4/issuetoc.
Topics: Hydrogen Sulfide; Protein S; Signal Transduction; Sulfides
PubMed: 30657595
DOI: 10.1111/bph.14579 -
Journal of the American Heart... Feb 2022Background Five classic thrombophilias have been recognized: factor V Leiden (rs6025), the prothrombin G20210A variant (rs1799963), and protein C, protein S, and...
Background Five classic thrombophilias have been recognized: factor V Leiden (rs6025), the prothrombin G20210A variant (rs1799963), and protein C, protein S, and antithrombin deficiencies. This study aimed to determine the thrombotic risk of classic thrombophilias in a cohort of middle-aged and older adults. Methods and Results Factor V Leiden, prothrombin G20210A and protein-coding variants in the (protein C), (protein S), and (antithrombin) anticoagulant genes were determined in 29 387 subjects (born 1923-1950, 60% women) who participated in the Malmö Diet and Cancer study (1991-1996). The Human Gene Mutation Database was used to define 68 disease-causing mutations. Patients were followed up from baseline until the first event of venous thromboembolism (VTE), death, or Dec 31, 2018. Carriership (n=908, 3.1%) for disease-causing mutations in the , , and genes was associated with incident VTE: Hazard ratio (HR) was 1.6 (95% CI, 1.3-1.9). Variants not in Human Gene Mutation Database were not linked to VTE (HR, 1.1; 95% CI, 0.8-1.5). Heterozygosity for rs6025 and rs1799963 was associated with incident VTE: HR, 1.8 (95% CI, 1.6-2.0) and HR, 1.6 (95% CI, 1.3-2.0), respectively. The HR for carrying 1 classical thrombophilia variant was 1.7 (95% CI, 1.6-1.9). HR was 3.9 (95% CI, 3.1-5.0) for carriers of ≥2 thrombophilia variants. Conclusions The 5 classic thrombophilias are associated with a dose-graded risk of VTE in middle-aged and older adults. Disease-causing variants in the , , and genes were more common than the rs1799963 variant but the conferred genetic risk was comparable with the rs6025 and rs1799963 variants.
Topics: Aged; Anticoagulants; Antithrombins; Cohort Studies; Factor V; Female; Humans; Male; Middle Aged; Mutation; Protein C; Protein S; Prothrombin; Risk Factors; Thrombophilia; Thrombosis; Venous Thromboembolism
PubMed: 35112923
DOI: 10.1161/JAHA.121.023018 -
Frontiers in Immunology 2024Protein S-palmitoylation is a reversible post-translational lipid modification that involves the addition of a 16-carbon palmitoyl group to a protein cysteine residue... (Review)
Review
Protein S-palmitoylation is a reversible post-translational lipid modification that involves the addition of a 16-carbon palmitoyl group to a protein cysteine residue via a thioester linkage. This modification plays a crucial role in the regulation protein localization, accumulation, secretion, stability, and function. Dysregulation of protein S-palmitoylation can disrupt cellular pathways and contribute to the development of various diseases, particularly cancers. Aberrant S-palmitoylation has been extensively studied and proven to be involved in tumor initiation and growth, metastasis, and apoptosis. In addition, emerging evidence suggests that protein S-palmitoylation may also have a potential role in immune modulation. Therefore, a comprehensive understanding of the regulatory mechanisms of S-palmitoylation in tumor cells and the tumor immune microenvironment is essential to improve our understanding of this process. In this review, we summarize the recent progress of S-palmitoylation in tumors and the tumor immune microenvironment, focusing on the S-palmitoylation modification of various proteins. Furthermore, we propose new ideas for immunotherapeutic strategies through S-palmitoylation intervention.
Topics: Humans; Lipoylation; Protein Processing, Post-Translational; Cysteine; Neoplasms; Tumor Microenvironment
PubMed: 38415253
DOI: 10.3389/fimmu.2024.1337478 -
Journal of Proteome Research Jan 2021Protein -acylation (commonly known as palmitoylation) is a widespread reversible lipid modification, which plays critical roles in regulating protein localization,... (Review)
Review
Protein -acylation (commonly known as palmitoylation) is a widespread reversible lipid modification, which plays critical roles in regulating protein localization, activity, stability, and complex formation. The deregulation of protein -acylation contributes to many diseases such as cancer and neurodegenerative disorders. The past decade has witnessed substantial progress in proteomic analysis of protein -acylation, which significantly advanced our understanding of -acylation biology. In this review, we summarized the techniques for the enrichment of -acylated proteins or peptides, critically reviewed proteomic studies of protein -acylation at eight different levels, and proposed major challenges for the -acylproteomics field. In summary, proteome-scale analysis of protein -acylation comes of age and will play increasingly important roles in discovering new disease mechanisms, biomarkers, and therapeutic targets.
Topics: Acylation; Lipoylation; Protein S; Proteome; Proteomics
PubMed: 33253586
DOI: 10.1021/acs.jproteome.0c00409