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Signal peptidase complex

About: Signal peptidase complex is a research topic. Over the lifetime, 72 publications have been published within this topic receiving 28599 citations.


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Journal ArticleDOI
TL;DR: A computer program that progressively evaluates the hydrophilicity and hydrophobicity of a protein along its amino acid sequence has been devised and its simplicity and its graphic nature make it a very useful tool for the evaluation of protein structures.

21,921 citations

Journal ArticleDOI
TL;DR: In this article, it was shown that in vitro completion of these nascent light chains resulted in the synthesis of some chains having the same mol wt as the authentic secreted light chain, because of completion of in vivo proteolytically processed chains and of other chains which, due to the completion of unprocessed chains, have the same moll wt, as the precursor of the light chain.
Abstract: Fractionation of MOPC 41 DL-1 tumors revealed that the mRNA for the light chain of immunoglobulin is localized exclusively in membrane-bound ribosomes. It was shown that the translation product of isolated light chain mRNA in a heterologous protein-synthesizing system in vitro is larger than the authentic secreted light chain; this confirms similar results from several laboratories. The synthesis in vitro of a precursor protein of the light chain is not an artifact of translation in a heterologous system, because it was shown that detached polysomes, isolated from detergent-treated rough microsomes, not only contain nascent light chains which have already been proteolytically processed in vivo but also contain unprocessed nascent light chains. In vitro completion of these nascent light chains thus resulted in the synthesis of some chains having the same mol wt as the authentic secreted light chains, because of completion of in vivo proteolytically processed chains and of other chains which, due to the completion of unprocessed chains, have the same mol wt as the precursor of the light chain. In contrast, completion of the nascent light chains contained in rough microsomes resulted in the synthesis of only processed light chains. Taken together, these results indicate that the processing activity is present in isolated rough microsomes, that it is localized in the membrane moiety of rough microsomes, and, therefore, that it was most likely solubilized during detergent treatment used for the isolation of detached polysomes. Furthermore, these results established that processing in vivo takes place before completion of the nascent chain. The data also indicate that in vitro processing of nascent chains by rough microsomes is dependent on ribosome binding to the membrane. If the latter process is interfered with by aurintricarboxylic acid, rough microsomes also synthesize some unprocessed chains. The data presented in this paper have been interpreted in the light of a recently proposed hypothesis. This hypothesis, referred to as the signal hypothesis, is described in greater detail in the Discussion section.

2,571 citations

Journal ArticleDOI
TL;DR: These results establish unequivocally that the information for segregation of a translation product is encoded in the mRNA itself, not in the protein- synthesizing apparatus; this provides strong evidence in support of the signal hypothesis.
Abstract: The data presented in this paper demonstrate that native small ribosomal subunits from reticulocytes (containing initiation factors) and large ribosomal subunits derived from free polysomes of reticulocytes by the puromycin-KCl procedures can function with stripped microsomes derived from dog pancreas rough microsomes in a protein-synthesizing system in vitro in response to added IgG light chain mRNA so as to segregate the translation product in a proteolysis-resistant space. No such segregation took place for the translation product of globin mRNA. In addition to their ability to segregate the translation product of a specific heterologous mRNA, native dog pancreas rough microsomes as well as derived stripped microsomes were able to proteolytically process the larger, primary translation product in an apparently correct manner, as evidenced by the identical mol wt of the segregated translation product and the authentic secreted light chain. Segregation as well as proteolytic processing by native and stripped microsomes occurred only during ongoing translation but not after completion of translation. Attempts to solubilize the proteolytic processing activity, presumably localized in the microsomal membrane by detergent treatment, and to achieve proteolytic processing of the completed light chain precursor protein failed. Taken together, these results establish unequivocally that the information for segregation of a translation product is encoded in the mRNA itself, not in the protein-synthesizing apparatus; this provides strong evidence in support of the signal hypothesis.

1,052 citations

Book ChapterDOI
TL;DR: This chapter describes a rapid isolation procedure that reproducibly yields highly active microsomal membranes, and presents method for refining the crude rough microsomes (RM) fraction by column washing, EDTA stripping, or nuclease treatment.
Abstract: Publisher Summary This chapter describes a rapid isolation procedure that reproducibly yields highly active microsomal membranes, and presents method for refining the crude rough microsomes (RM) fraction by column washing, EDTA stripping, or nuclease treatment. The column-washed RM has almost no inhibitory effects on protein synthesis; EDTA-stripped RM has a high specific activity, because of removal of ribosomes and proteins; nuclease-treated RM has essentially no endogenous mRNA activity. All these microsome preparations still contain signal recognition particle (SRP). They are, therefore, translocation-active in wheat germ as well as reticulocyte lysate. Most of the microsome preparations are glycosylation active, but there is a high variability from preparation to preparation in the extent of glycosylation obtained. Microsomal membranes from sources other than dog pancreas are also employed in cotranslational studies, and the most successfully used alternative systems are probably chicken oviduct RM and adrenal microsomes.

643 citations

Journal ArticleDOI
07 Jul 2016-Nature
TL;DR: It is found that SPCS1 dependence could be bypassed by replacing the native prM protein leader sequences with a class I major histocompatibility complex (MHC) antigen leader sequence, and Flaviviridae have a unique dependence on this signal peptide processing pathway.
Abstract: Flaviviruses infect hundreds of millions of people annually, and no antiviral therapy is available. We performed a genome-wide CRISPR/Cas9-based screen to identify host genes that, when edited, resulted in reduced flavivirus infection. Here, we validated nine human genes required for flavivirus infectivity, and these were associated with endoplasmic reticulum functions including translocation, protein degradation, and N-linked glycosylation. In particular, a subset of endoplasmic reticulum-associated signal peptidase complex (SPCS) proteins was necessary for proper cleavage of the flavivirus structural proteins (prM and E) and secretion of viral particles. Loss of SPCS1 expression resulted in markedly reduced yield of all Flaviviridae family members tested (West Nile, Dengue, Zika, yellow fever, Japanese encephalitis, and hepatitis C viruses), but had little impact on alphavirus, bunyavirus, or rhabdovirus infection or the surface expression or secretion of diverse host proteins. We found that SPCS1 dependence could be bypassed by replacing the native prM protein leader sequences with a class I major histocompatibility complex (MHC) antigen leader sequence. Thus, SPCS1, either directly or indirectly via its interactions with unknown host proteins, preferentially promotes the processing of specific protein cargo, and Flaviviridae have a unique dependence on this signal peptide processing pathway. SPCS1 and other signal processing pathway members could represent pharmacological targets for inhibiting infection by the expanding number of flaviviruses of medical concern.

317 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20216
20203
20196
20183
20162
20151