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Improved secretion of glycoproteins using an N-glycan-restricted passport sequence tag recognized by cargo receptor
- Source :
- Nature Communications, Vol 11, Iss 1, Pp 1-9 (2020), Nature Communications
- Publication Year :
- 2020
- Publisher :
- Nature Publishing Group, 2020.
-
Abstract
- 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.<br />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).
- Subjects :
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 11
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....7a8b35a1869315c9ade7fa6e1a35db5d