Improved secretion of glycoproteins using an N-glycan-restricted passport sequence tag recognized by cargo receptor
| Autor: | Satoshi Ninagawa, Taiki Saito, Hirokazu Yagi, Miho Nishio, Takahiro Anzai, Yukiko Kamiya, Mahito Nakanishi, Koichi Kato, Kazuhiro Aoki, Tadashi Satoh, Honda Rena, Yusaku Ohta, Kousuke Suzuki, Maho Yagi-Utsumi |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Receptor complex animal diseases Glycobiology Vesicular Transport Proteins General Physics and Astronomy Golgi Apparatus Endoplasmic Reticulum Biochemistry law.invention 0302 clinical medicine law hemic and lymphatic diseases lcsh:Science Peptide sequence chemistry.chemical_classification Multidisciplinary Secretory Pathway biology Chemistry Cell biology Transport protein Protein Transport Recombinant DNA Structural biology Glycan congenital hereditary and neonatal diseases and abnormalities Science Carbohydrates General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Polysaccharides Humans Secretion Amino Acid Sequence Erythropoietin Secretory pathway Glycoproteins Factor VIII Proteins Factor V Membrane Proteins General Chemistry 030104 developmental biology Mannose-Binding Lectins biology.protein lcsh:Q Glycoprotein Carrier Proteins 030217 neurology & neurosurgery |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-9 (2020) Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-020-15192-1 |
| Popis: | MCFD2 and ERGIC-53, which are the products of causative genes of combined factor V and factor VIII deficiency, form a cargo receptor complex responsible for intracellular transport of these coagulation factors in the early secretory pathway. In this study, using an NMR technique, we successfully identified an MCFD2-binding segment from factor VIII composed of a 10 amino acid sequence that enhances its secretion. This prompted us to examine possible effects of attaching this sequence to recombinant glycoproteins on their secretion. We found that the secretion level of recombinant erythropoietin was significantly increased simply by tagging it with the passport sequence. Our findings not only provide molecular basis for the intracellular trafficking of coagulation factors and their genetic deficiency but also offer a potentially useful tool for increasing the production yields of recombinant glycoproteins of biopharmaceutical interest. The secretion of blood coagulation factor V and factor VIII (FV and FVIII) are driven by secretion factors ERGIC-53 and MCDF2. Here, the authors report a 10 amino acid motif from FVIII that can enhance secretion of another glycoprotein erythropoietin (EPO). |
| Databáze: | OpenAIRE |
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