Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the amino acid sequence requirements for intracellular cleavage of the Rous sarcoma virus glycoprotein precursor by introducing mutations into the region encoding the cleavage recognition site (Arg-Arg-Lys-Arg). In addition to mutants G1 (Arg-Arg-Glu-Arg) and Dr1 (deletion of all four codons) that we have reported on previously (L. G. Perez and E. Hunter, J. Virol. 61:1609-1614, 1987), we constructed two additional mutants, AR1 (Arg-Arg-Arg-Arg), in which the highly conserved lysine is replaced by an arginine, and S19 (Ser-Arg-Glu-Arg), in which no dibasic pairs remain. The results of these studies demonstrate that when the cleavage sequence is deleted (Dr1) or modified to contain unpaired basic residues (S19), intracellular cleavage of the glycoprotein precursor is completely blocked. This demonstrates that the cellular endopeptidase responsible for cleavage has a stringent requirement for the presence of a pair of basic residues (Arg-Arg or Lys-Arg). Furthermore, it implies that the cleavage enzyme is not trypsinlike, since it is unable to recognize arginine residues that are sensitive to trypsin action. Substitution of the mutated genes into a replication-competent avian retrovirus genome showed that cleavage of the glycoprotein precursor was not required for incorporation into virions but was necessary for infectivity. Treatment of BH-RCAN-S19-transfected turkey cells with low levels of trypsin resulted in the release of infectious virus, demonstrating that exogenous cleavage could generate a biologically active glycoprotein molecule.
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PMID:Mutations within the proteolytic cleavage site of the Rous sarcoma virus glycoprotein define a requirement for dibasic residues for intracellular cleavage. 137 May 59

We have investigated the specificity of the proteolytic cleavage of the Rous sarcoma virus glycoprotein precursor by introducing two mutations into the putative cleavage region (Arg-Arg-Lys-Arg). We show that neither a deletion of the cleavage sequence nor a glutamic acid for lysine substitution altered intracellular transport or surface expression of the env gene products. However, both the four-amino-acid deletion and the glutamic acid substitution block processing of the env precursor. Susceptibility of the glutamic acid-substituted env precursor to proteases indicated that tertiary protein structure was unaffected. While inhibitor experiments suggested that more than one endopeptidase might be capable of mediating the proteolytic cleavage, the results presented here point to the presence in the Golgi apparatus of a novel endopeptidase, required for retroviral glycoprotein cleavage, that has a high specificity for lysine-containing peptides.
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PMID:Mutations within the proteolytic cleavage site of the Rous sarcoma virus glycoprotein that block processing to gp85 and gp37. 303 86

A chymostatin-sensitive step in the release of plasminogen activator from transformed fibroblasts has been described recently. By using synthetic peptidyl substrates, we have detected and characterized a chymostatin-sensitive peptidase activity in chicken embryo fibroblasts transformed by Rous sarcoma virus. The activity represents a neutral endopeptidase that exhibits phenylalanine specificity and is inhibited by diisopropyl fluorophosphate. A detailed inhibitor profile of the enzyme activity shows that it is distinct from other chymotrypsin-like phenylalanine-preferring peptidases. The endopeptidase activity in transformed fibroblasts is increased over that of parallel cultures of normal fibroblasts. The mechanism of enzyme inhibition by chymostatin is indicated by these studies, and the possible role of the enzyme in modulating plasminogen activator secretion is discussed.
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PMID:Detection and partial characterization of a chymostatin-sensitive endopeptidase in transformed fibroblasts. 630 Aug 32

Retroviruses assemble new virus particles that are released by budding from the plasma membranes of infected cells. Gag proteins, encoded by retroviruses, orchestrate the assembly of virus particles in close collaboration with host cell machinery. The earliest steps in retrovirus assembly-those immediately following synthesis of Gag on cytosolic ribosomes-are poorly understood. Rous sarcoma virus (RSV) offers a unique model system for dissecting these early steps because the RSV Gag protein undergoes transient nuclear trafficking prior to plasma membrane transport. Other Gag proteins, including those of human immunodeficiency virus (HIV), murine leukemia virus (MLV), foamy virus and retrotransposons in Schizosaccharomyces pombe and Drosophila, have also been detected in the nucleus, suggesting that nuclear trafficking of Gag proteins is a common property of retroviruses and retrotransposons. In addition to retroviruses, many structural proteins of unrelated viruses, including influenza M1, NEP and NP proteins,38 Borna disease virus N and P proteins28,56 and coronavirus N protein,23,57 undergo nuclear localization and bind viral RNAs to form viral ribonuclear protein (RNP) complexes that are exported from the nucleus for packaging into virus particles. Similarly, nuclear trafficking of the RSV Gag protein is required for efficient encapsidation of the viral genomic RNA (gRNA) into assembling virus particles.19 Recently, we reported that the viral RNA itself appears to be a key factor in controlling the nucleus/cytosol distribution of RSV Gag.22 Our data demonstrate that binding of RSV RNA to the Gag protein promotes Gag-CRM1-RanGTP binding, resulting in export of the retroviral RNP from the nucleus. We propose that association of the viral RNA induces a conformational change in Gag that reveals its nuclear export signal (NES) and prepares that complex for its journey to the plasma membrane for budding. This work challenges existing dogmas regarding the molecular basis of Gag-mediated selection of gRNA for packaging and may lead to novel paradigms for the mechanism of retroviral genome encapsidation.
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PMID:New insights into the nuclear localization of retroviral Gag proteins. 2173 31