Topic
Protein maturation
About: Protein maturation is a research topic. Over the lifetime, 613 publications have been published within this topic receiving 29222 citations.
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15 Jan 2001
TL;DR: P.H. North: Prevention of unwanted proteolysis V.V.C. Price: Proteinase as probes of conformation J.M. Pratt: Proteases as membrane probes P.E. Butler: Solubilization of membrane proteins P.B. Neurath: The diversity of proteolytic enzymes G. DeMartino, R.S. Sarath, & F. Wagner : Proteax assay methods.
Abstract: H. Neurath: The diversity of proteolytic enzymes G. DeMartino: Purification of proteolytic enzymes G. Sarath, R.S. de la Motte, & F. Wagner: Proteax assay methods B.M. Dunn: Determination of protease mechanism G. Salvesen: Inhibition of proteolytic enzymes M.H. North: Prevention of unwanted proteolysis V. Kasche: Proteases in peptide synthesis A.V. Flannery, R.J. Beynon, & J.S. Bond: Proteolysis of proteins for sequence analysis N.C. Price: Proteinase as probes of conformation J.M. Pratt: Proteases as membrane probes P.E. Butler: Solubilization of membrane proteins P.B. Gordon: Exogenous control of catabolism N.P. Birch: Proteases in protein maturation
816 citations
TL;DR: The data suggest that a reduction in frataxin results in oxidative damage, given the shared clinical features between Friedreich ataxia, vitamin E deficiency and some mitochondriopathies.
Abstract: Friedreich ataxia is a progressive neurodegenerative disorder caused by loss of function mutations in the frataxin gene. In order to unravel frataxin function we developed monoclonal antibodies raised against different regions of the protein. These antibodies detect a processed 18 kDa protein in various human and mouse tissues and cell lines that is severely reduced in Friedreich ataxia patients. By immunocytofluorescence and immunocytoelectron microscopy we show that frataxin is located in mitochondria, associated with the mitochondrial membranes and crests. Analysis of cellular localization of various truncated forms of frataxin expressed in cultured cells and evidence of removal of an N-terminal epitope during protein maturation demonstrated that the mitochondrial targetting sequence is encoded by the first 20 amino acids. Given the shared clinical features between Friedreich ataxia, vitamin E deficiency and some mitochondriopathies, our data suggest that a reduction in frataxin results in oxidative damage.
693 citations
TL;DR: It is reported that enforced expression of XBP1(S) is sufficient to induce synthesis of phosphatidylcholine, the primary phospholipid of the ER membrane, and this data suggest that XBP2(S), the active form of the XBP 1 transcription factor generated by UPR-mediated splicing of X BP1 mRNA, links the mammalian UPR to phospholIPid biosynthesis and ER biogenesis.
Abstract: When the protein folding capacity of the endoplasmic reticulum (ER) is challenged, the unfolded protein response (UPR) maintains ER homeostasis by regulating protein synthesis and enhancing expression of resident ER proteins that facilitate protein maturation and degradation. Here, we report that enforced expression of XBP1(S), the active form of the XBP1 transcription factor generated by UPR-mediated splicing of XBP1 mRNA, is sufficient to induce synthesis of phosphatidylcholine, the primary phospholipid of the ER membrane. Cells overexpressing XBP1(S) exhibit elevated levels of membrane phospholipids, increased surface area and volume of rough ER, and enhanced activity of the cytidine diphosphocholine pathway of phosphatidylcholine biosynthesis. These data suggest that XBP1(S) links the mammalian UPR to phospholipid biosynthesis and ER biogenesis.
642 citations
TL;DR: Analysis of the human genome reveals that approximately a third of all open reading frames code for proteins that enter the endoplasmic reticulum (ER), demonstrating the importance of this organelle for global protein maturation.
Abstract: Analysis of the human genome reveals that approximately a third of all open reading frames code for proteins that enter the endoplasmic reticulum (ER), demonstrating the importance of this organelle for global protein maturation. The path taken by a polypeptide through the secretory pathway starts with its translocation across or into the ER membrane. It then must fold and be modified correctly in the ER before being transported via the Golgi apparatus to the cell surface or another destination. Being physically segregated from the cytosol means that the ER lumen has a distinct folding environment. It contains much of the machinery for fulfilling the task of protein production, including complex pathways for folding, assembly, modification, quality control, and recycling. Importantly, the compartmentalization means that several modifications that do not occur in the cytosol, such as glycosylation and extensive disulfide bond formation, can occur to secreted proteins to enhance their stability before their exposure to the extracellular milieu. How these various machineries interact during the normal pathway of folding and protein secretion is the subject of this review.
595 citations
TL;DR: Calnexin, an endoplasmic reticulum transmembrane protein, represents a new type of molecular chaperone that selectively associates in a transient fashion with newly synthesized monomeric glycoproteins in HepG2 cells.
Abstract: Calnexin, an endoplasmic reticulum transmembrane protein, represents a new type of molecular chaperone that selectively associates in a transient fashion with newly synthesized monomeric glycoproteins in HepG2 cells. Calnexin only recognizes glycoproteins when they are incompletely folded. Dissociation of glycoproteins from calnexin occurs at different rates and is related to the time taken for their folding, which may then initiate their differential transport rates from the endoplasmic reticulum.
539 citations