A stop transfer sequence recognizes receptors for nascent chain translocation across the endoplasmic reticulum membrane |
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| Authors: | N K Mize D W Andrews V R Lingappa |
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| Affiliation: | 1. Department of Physiology University of California, San Francisco San Francisco, California 94143 USA;2. Department of Medicine University of California, San Francisco San Francisco, California 94143 USA;3. Topogen San Francisco, California 94143 USA;1. Department of Biology, Loyola University Chicago, United States;2. Engineering Science Program, Loyola University Chicago, United States;1. Mechanobiology Institute, National University of Singapore, Singapore;2. Department of Biomedical Engineering, National University of Singapore, Singapore;1. Molecular Neuropharmacology and Genetics Laboratory, Lundbeck Foundation Center for Biomembranes in Nanomedicine, Department of Neuroscience, Faculty of Health and Medical Sciences, The Panum Institute - Mærsk Tower, University of Copenhagen, 2200 Copenhagen N, Denmark;2. Bionanotechnology and Nanomedicine Laboratory, Lundbeck Foundation Center for Biomembranes in Nanomedicine, Department of Chemistry, and Nano-Science Center, University of Copenhagen, 2300 Copenhagen Ø, Denmark;3. Department of Physiology and Biophysics, Weill Cornell Medical College, Cornell University, 1300 York Avenue, New York City, NY 10065, USA;1. Department of Laboratory Medicine, Zhongshan Hospital of Sun Yat-sen University, 2 Sunwendong Road, Zhongshan 528403, Guangdong, China;2. Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, 2 Zhongshan Road, Guangzhou 510080, Guangdong, China;1. Department of Biology, New York University, New York, NY 10003, USA;2. Center for Genomics and Systems Biology, New York University, New York, NY 10003, USA;3. Center for Genomics and Systems Biology, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates;4. Duke Center for Genomic and Computational Biology, Duke University, Durham, NC 27708, USA;5. Department of Biology, Duke University, Durham, NC 27708, USA |
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| Abstract: | A stop transfer sequence derived from the extreme carboxyl terminus of membrane IgM heavy chain has been shown to confer predictable transmembrane orientation to secretory proteins by aborting translocation of subsequently synthesized protein domains. Here we demonstrate that, in certain peptide sequence contexts, the same stop transfer sequence is also capable of initiating domain translocation across the endoplasmic reticulum (ER) membrane. Translocation directed by a stop transfer sequence is similar to, but distinguishable from, the action of a conventional signal sequence. Translocation is dependent on participation of the ribosome and protein receptors both in the cytoplasm and in the ER membrane. Moreover, both amino- and carboxy-terminal flanking protein domains can be translocated. Unlike a signal sequence, the stop transfer sequence is not itself translocated across the membrane. These results have implications for the nature of signal sequences, stop transfer sequences, and their receptor interactions. |
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