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Journal of Biochemistry Jun 1998The intracellular sorting of newly synthesized precursor proteins (preproteins) to mitochondria depends on the "mitochondria-targeting sequence" (MTS), which is located... (Review)
Review
The intracellular sorting of newly synthesized precursor proteins (preproteins) to mitochondria depends on the "mitochondria-targeting sequence" (MTS), which is located at the amino termini of the preproteins. MTS is required, however, not only for targeting newly synthesized preproteins to mitochondria, but also for all the following steps along the mitochondrial protein import pathway. MTS of nascent preproteins is first recognized by a cytoplasmic molecular chaperone, MSF, and then by Tom70 and Tom20 of the mitochondrial outer membrane receptor complex, Tom5 and Tom40 of the outer membrane protein translocation machinery, Tim23 of the inner membrane protein translocation machinery, and finally the processing peptidase, MPP, in the matrix. MTS is a multi-role sorting sequence which specifically interacts with various components along the mitochondrial protein import pathway. Recognition of MTS at multiple steps during the import of preproteins may contribute to the strict sorting of proteins destined for mitochondria.
Topics: 14-3-3 Proteins; Amino Acid Sequence; Animals; Biological Transport; Carrier Proteins; Fungal Proteins; Humans; Membrane Proteins; Membrane Transport Proteins; Mitochondria; Mitochondrial Membrane Transport Proteins; Mitochondrial Precursor Protein Import Complex Proteins; Molecular Chaperones; Molecular Sequence Data; Proteins; Receptors, Cell Surface; Receptors, Cytoplasmic and Nuclear; Saccharomyces cerevisiae Proteins; Sequence Analysis
PubMed: 9603986
DOI: 10.1093/oxfordjournals.jbchem.a022036 -
Annals of Laboratory Medicine Jan 2013Thrombophilia that is common among Caucasians is caused by genetic polymorphisms of coagulation factor V Leiden (R506Q) and prothrombin G20210A. Unlike that in... (Review)
Review
Thrombophilia that is common among Caucasians is caused by genetic polymorphisms of coagulation factor V Leiden (R506Q) and prothrombin G20210A. Unlike that in Caucasians, thrombophilia that is common in the Japanese and Chinese involve dysfunction of the activated protein C (APC) anticoagulant system caused by abnormal protein S and protein C molecules. Approximately 50% of Japanese and Chinese individuals who develop venous thrombosis have reduced activities of protein S. The abnormal sites causing the protein S molecule abnormalities are distributed throughout the protein S gene, PROS1. One of the most common abnormalities is protein S Tokushima (K155E), which accounts for about 30% of the protein S molecule abnormalities in the Japanese. Whether APC dysfunction occurs in other Asian countries is an important aspect of mapping thrombophilia among Asians. International surveys using an accurate assay system are needed to determine this.
Topics: Asian People; Blood Coagulation; Blood Proteins; Humans; Protein C; Protein S; Thrombophilia; Venous Thrombosis
PubMed: 23301217
DOI: 10.3343/alm.2013.33.1.8 -
IUBMB Life 2001Most mitochondrial proteins are encoded by the nuclear genome and thus have to be imported into mitochondria from the cytosol. Protein translocation across and into the... (Review)
Review
Most mitochondrial proteins are encoded by the nuclear genome and thus have to be imported into mitochondria from the cytosol. Protein translocation across and into the mitochondrial membranes is a multistep process facilitated by the coordinated action of at least four specialized translocation systems in the outer and inner membranes of mitochondria. The outer membrane contains one general translocase, the TOM complex, whereas three distinct translocases are located in the inner membrane, which facilitates translocation of different classes of preproteins. The TIM23 complex mediates import of matrix-targeted preproteins with N-terminal presequences, whereas hydrophobic preproteins with internal targeting signals are inserted into the inner membrane via the TIM22 complex. The OXA translocase mediates the insertion of preproteins from the matrix space into the inner membrane. This review focuses on the structural organization and function of the import machinery of the model organisms of Saccharomyces cerevisiae and Neurospora crassa. In addition, the molecular basis of a new human mitochondrial disorder is discussed, the Mohr-Tranebjaerg syndrome. This is the first known disease, which is caused by an impaired mitochondrial protein import machinery leading to progressive neurodegeneration.
Topics: Animals; Carrier Proteins; Humans; Intracellular Membranes; Macromolecular Substances; Membrane Proteins; Membrane Transport Proteins; Mitochondria; Mitochondrial Membrane Transport Proteins; Mitochondrial Precursor Protein Import Complex Proteins; Mitochondrial Proteins; Protein Transport; Saccharomyces cerevisiae Proteins; Signal Transduction
PubMed: 11798021
DOI: 10.1080/15216540152845894 -
Thrombosis Research 2008Protein S is a vitamin K-dependent protein that acts as a cofactor of the anticoagulant protein APC. However, protein S also exhibits anticoagulant activity in the... (Review)
Review
Protein S is a vitamin K-dependent protein that acts as a cofactor of the anticoagulant protein APC. However, protein S also exhibits anticoagulant activity in the absence of APC. Thrombin generation experiments in normal plasma and in plasma deficient in tissue factor pathway inhibitor (TFPI) and/or protein S demonstrated that protein S stimulates the inhibition of TF by TFPI. Kinetic analysis in model systems containing purified proteins showed that protein S enhances the formation of the binary FXa:TFPI complex by reducing the Ki of TFPI from approximately 4 nM to approximately 0.5 nM. Enhancement of inhibitory activity of TFPI by protein S is only observed with full-length TFPI and in the presence of a negatively charged phospholipid surface. The Ki decrease brings the TFPI concentration necessary for FXa:TFPI complex formation within range of the plasma TFPI concentration which increases FXa:TFPI complex formation and accelerates feedback inhibition of the TF pathway by enhancing the formation of the quaternary TFPI:FXa:TF:FVIIa complex. Thus, protein S is not only a cofactor of APC, but also of TFPI. A reduced TFPI cofactor activity may contribute to the increased risk of venous thrombosis in protein-S deficient individuals. Using calibrated automated thrombography we have developed two assays that enable quantification of the functional activity of the TFPI/protein S system in plasma. These assays show that the activity of the TFPI/protein S system is greatly impaired in oral contraceptive users.
Topics: Blood Coagulation Factors; Factor Xa Inhibitors; Humans; Kinetics; Lipoproteins; Protein S; Receptors, Cell Surface; Thrombin; Thromboplastin; Thrombosis
PubMed: 18691502
DOI: 10.1016/S0049-3848(08)70021-5 -
Proceedings of the Society For... Jul 1992
Review
Topics: Adult; Carrier Proteins; Complement Inactivator Proteins; Female; Glycoproteins; Humans; Infant, Newborn; Molecular Structure; Pregnancy; Protein S; Reference Values; Thrombosis
PubMed: 1535444
DOI: 10.3181/00379727-200-43435 -
Current Biology : CB Sep 2004A cell-free system has been developed in budding yeast that provides direct evidence that the Dsk2/Dph1, Rad23/Rhp23 and Rpn10/Pus1 multi-ubiquitin-binding proteins,... (Review)
Review
A cell-free system has been developed in budding yeast that provides direct evidence that the Dsk2/Dph1, Rad23/Rhp23 and Rpn10/Pus1 multi-ubiquitin-binding proteins, long implicated in substrate recognition and presentation to the 26S proteasome, actually fulfil such a role.
Topics: Carrier Proteins; Cell Cycle Proteins; Cyclin-Dependent Kinase Inhibitor Proteins; DNA-Binding Proteins; Models, Biological; Proteasome Endopeptidase Complex; Protein Binding; Proteins; Saccharomyces cerevisiae Proteins; Schizosaccharomyces pombe Proteins; Ubiquitins; Yeasts
PubMed: 15380085
DOI: 10.1016/j.cub.2004.09.012 -
Seminars in Cell & Developmental Biology Oct 1998Vesicular traffic within the early secretory pathway is mediated by COPI- and COPII-coated vesicles. While COPII-coated vesicles appear to be involved exclusively in the... (Review)
Review
Vesicular traffic within the early secretory pathway is mediated by COPI- and COPII-coated vesicles. While COPII-coated vesicles appear to be involved exclusively in the export of secretory proteins and lipids from the endoplasmic reticulum (ER), COPI-coated vesicles seem to function in both anterograde and retrograde transport between the ER-Golgi intermediate compartment (IC) and the Golgi as well as in intra-Golgi transport. Here, we focus on (i) the mechanisms how these transport carriers are formed from a given donor membrane; and (ii) the possible mechanisms involved in sorting of proteins and lipids into such transport vesicles.
Topics: Biological Transport; COP-Coated Vesicles; Carrier Proteins; Cholesterol; Coated Vesicles; Coatomer Protein; Endoplasmic Reticulum, Rough; Eukaryotic Cells; Fungal Proteins; GTP-Binding Proteins; GTPase-Activating Proteins; Golgi Apparatus; Guanosine Triphosphate; Macromolecular Substances; Membrane Lipids; Membrane Proteins; Models, Biological; Monomeric GTP-Binding Proteins; Nuclear Pore Complex Proteins; Phosphoproteins; Proteins; Saccharomyces cerevisiae Proteins; Sphingomyelins; Vesicular Transport Proteins
PubMed: 9835636
DOI: 10.1006/scdb.1998.0256 -
Thrombosis and Haemostasis Jul 1991The protein C anticoagulant system provides important control of the blood coagulation cascade. The key protein is protein C, a vitamin K-dependent zymogen which is... (Review)
Review
The protein C anticoagulant system provides important control of the blood coagulation cascade. The key protein is protein C, a vitamin K-dependent zymogen which is activated to a serine protease by the thrombin-thrombomodulin complex on endothelial cells. Activated protein C functions by degrading the phospholipid-bound coagulation factors Va and VIIIa. Protein S is a cofactor in these reactions. It is a vitamin K-dependent protein with multiple domains. From the N-terminal it contains a vitamin K-dependent domain, a thrombin-sensitive region, four EGF) epidermal growth factor (EGF)-like domains and a C-terminal region homologous to the androgen binding proteins. Three different types of post-translationally modified amino acid residues are found in protein S, 11 gamma-carboxy glutamic acid residues in the vitamin K-dependent domain, a beta-hydroxylated aspartic acid in the first EGF-like domain and a beta-hydroxylated asparagine in each of the other three EGF-like domains. The EGF-like domains contain very high affinity calcium binding sites, and calcium plays a structural and stabilising role. The importance of the anticoagulant properties of protein S is illustrated by the high incidence of thrombo-embolic events in individuals with heterozygous deficiency. Anticoagulation may not be the sole function of protein S, since both in vivo and in vitro, it forms a high affinity non-covalent complex with one of the regulatory proteins in the complement system, the C4b-binding protein (C4BP). The complexed form of protein S has no APC cofactor function. C4BP is a high molecular weight multimeric protein with a unique octopus-like structure. It is composed of seven identical alpha-chains and one beta-chain. The alpha- and beta-chains are linked by disulphide bridges. The cDNA cloning of the beta-chain showed the alpha- and beta-chains to be homologous and of common evolutionary origin. Both subunits are composed of multiple 60 amino acid long repeats (short complement or consensus repeats, SCR) and their genes are located in close proximity on chromosome 1, band 1q32. Available experimental data suggest the beta-chain to contain the single protein S binding site on C4BP, whereas each of the alpha-chains contains a binding site for the complement protein, C4b. As C4BP lacking the beta-chain is unable to bind protein S, the beta-chain is required for protein S binding, but not for the assembly of the alpha-chains during biosynthesis.(ABSTRACT TRUNCATED AT 400 WORDS)
Topics: Amino Acid Sequence; Animals; Blood Coagulation; Carrier Proteins; Complement C4b; Complement Inactivator Proteins; Epidermal Growth Factor; Glycoproteins; Humans; Molecular Sequence Data; Protein C; Protein S; Serum Amyloid P-Component
PubMed: 1833851
DOI: No ID Found -
Handbook of Experimental Pharmacology 2017Nitric oxide (NO) raises the intracellular 3',5'-cyclic guanosine monophosphate (cGMP) level through the activation of soluble guanylate cyclase and, in the presence of... (Review)
Review
Nitric oxide (NO) raises the intracellular 3',5'-cyclic guanosine monophosphate (cGMP) level through the activation of soluble guanylate cyclase and, in the presence of reactive oxygen species (ROS), reacts with biomolecules to produce nitrated cGMP derivatives. 8-Nitro-cGMP was the first endogenous cGMP derivative discovered in mammalian cells (2007) and was later found in plant cells. Among the six nitrogen atoms in this molecule, the one in the nitro group (NO) comes from NO. This chapter asserts that this newly found cGMP is undoubtedly one of the major physiological cNMPs. Multiple studies suggest that its intracellular abundance might exceed that of unmodified cGMP. The characteristic chemical feature of 8-nitro-cGMP is its ability to modify proteinous cysteine residues via a stable sulfide bond. In this posttranslational modification, the nitro group is detached from the guanine base. This modification, termed "protein S-guanylation," is known to regulate the physiological functions of several important proteins. Furthermore, 8-nitro-cGMP participates in the regulation of autophagy. For example, in antibacterial autophagy (xenophagy), S-guanylation accumulates around invading bacterial cells and functions as a "tag" for subsequent clearance of the organism via ubiquitin modifications. This finding suggests the existence of a system for recognizing the cGMP structure on proteins. Autophagy induction by 8-nitro-cGMP is mechanistically distinct from the well-described starvation-induced autophagy and is independent of the action of mTOR, the master regulator of canonical autophagy.
Topics: Animals; Autophagy; Cell Proliferation; Cellular Senescence; Cyclic GMP; Cyclic GMP-Dependent Protein Kinases; Humans; Molecular Structure; Protein Processing, Post-Translational; Second Messenger Systems
PubMed: 28213625
DOI: 10.1007/164_2016_5000 -
Cellular and Molecular Life Sciences :... Nov 2001The yeast prions represent a very attractive and tractable model for investigating the prion world. The more extensively studied yeast prion [PSI] leads to a propagation... (Review)
Review
The yeast prions represent a very attractive and tractable model for investigating the prion world. The more extensively studied yeast prion [PSI] leads to a propagation model that links auto-aggregation in amyloid formation and inactivation of the cellular function of the yeast 'prion protein' Sup35p. The other prion model, [URE3], appears to be similar in some genetic and biochemical properties. The characterisation of both Sup35p and Ure2p, the two 'prion proteins', mainly focusing on their aggregation properties, support this model. However, some important differences still exist that should be examined carefully. In particular, we have shown that Ure2p aggregation in vivo (monitored by fluorescence of Ure2-GFP fusion) does not necessarily give rise to a [URE3] phenotype. Comparisons of these two systems as well as more recent experiments are discussed in this review.
Topics: Animals; Fungal Proteins; Glutathione Peroxidase; Green Fluorescent Proteins; HSP70 Heat-Shock Proteins; Heat-Shock Proteins; Luminescent Proteins; Models, Biological; Peptide Termination Factors; Phenotype; Prions; Recombinant Fusion Proteins; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
PubMed: 11766884
DOI: 10.1007/PL00000823