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Efficient IgM assembly and secretion require the plasma cell induced endoplasmic reticulum protein pERp1

机译:有效的IgM组装和分泌需要浆细胞诱导的内质网蛋白pERp1

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摘要

Plasma cells daily secrete their own mass in antibodies, which fold and assemble in the endoplasmic reticulum (ER). To reach these levels, cells require pERpi, a novel lymphocyte-specific small ER-resident protein, which attains expression levels as high as BiP when B cells differentiate into plasma cells. Although pERpi has no homology with known ER proteins, it does contain a CXXC motif typical for oxidoreductases. In steady state, the CXXC cysteines are locked by two parallel disulfide bonds with a downstream C(X)_6C motif, and pERpi displays only modest oxidoreductase activity. pERpi emerged as a dedicated folding factor for IgM, associating with both heavy and light chains and promoting assembly and secretion of mature IgM.
机译:浆细胞每天分泌自己的抗体质量,这些抗体在内质网(ER)中折叠和组装。为了达到这些水平,细胞需要pERpi,一种新型的淋巴细胞特异性小ER驻留蛋白,当B细胞分化为浆细胞时,其表达水平高达BiP。尽管pERpi与已知的ER蛋白没有同源性,但它确实含有典型的氧化还原酶CXXC基序。在稳定状态下,CXXC半胱氨酸被两个具有下游C(X)_6C基序的平行二硫键锁定,而pERpi仅显示适度的氧化还原酶活性。 pERpi成为IgM的专用折叠因子,与重链和轻链相关联,并促进成熟IgM的组装和分泌。

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    Cellular Protein Chemistry, Bijvoet Center for Biomolecular Research, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158-2517;

    Cellular Protein Chemistry, Bijvoet Center for Biomolecular Research, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands;

    Cellular Protein Chemistry, Bijvoet Center for Biomolecular Research, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands CrossBeta (BV), Padualaan 8, 3584 CH Utrecht, The Netherlands;

    Cellular Protein Chemistry, Bijvoet Center for Biomolecular Research, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 0QH,United Kingdom;

    Biomolecular Mass Spectrometry, Bijvoet Center for Biomolecular Research, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands Philips Research, Prof. Holstlaan 4, 5656 AA Eindhoven, The Netherlands;

    Institute of Molecular Biology and Biophysics, Eidgenoessische Technische Hochschule, 8093 Zurich, Switzerland F. Hoffmann-La Roche Ltd., Formulation R&D Biologics, Pharmaceutical and Analytical R&D, 4070 Basel, Switzerland;

    Cell Microscopy Center, Department of Cell Biology and Institute of Biomembranes, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands;

    Department of Microbiology and Molecular Medicine, University of Geneva, CH-1211 Geneva, Switzerland Institute for Research in Biomedicine, CH-6500 Bellinzona,Switzerland;

    Cellular Protein Chemistry, Bijvoet Center for Biomolecular Research, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands;

    Cellular Protein Chemistry, Bijvoet Center for Biomolecular Research, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands Institute of Biotechnology, University of Helsinki, 00014 Helsinki, Finland;

    Cellular Protein Chemistry, Bijvoet Center for Biomolecular Research, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands;

    Institute of Molecular Biology and Biophysics, Eidgenoessische Technische Hochschule, 8093 Zurich, Switzerland;

    Cell Microscopy Center, Department of Cell Biology and Institute of Biomembranes, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands;

    Biomolecular Mass Spectrometry, Bijvoet Center for Biomolecular Research, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands;

    Department of Microbiology and Molecular Medicine, University of Geneva, CH-1211 Geneva, Switzerland Institute for Research in Biomedicine, CH-6500 Bellinzona,Switzerland;

    Cellular Protein Chemistry, Bijvoet Center for Biomolecular Research, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands;

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  • 入库时间 2022-08-18 00:42:06

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