A 30-Amino Acid Truncation of the Microsomal Triglyceride Transfer Protein Large Subunit Disrupts Its Interaction with Protein Disulfide-isomerase and Causes Abetalipoproteinemia
| العنوان: | A 30-Amino Acid Truncation of the Microsomal Triglyceride Transfer Protein Large Subunit Disrupts Its Interaction with Protein Disulfide-isomerase and Causes Abetalipoproteinemia |
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| المؤلفون: | Connie Smith-Monroy, Beverly Ricci, Gordon William Robinson, Laura Blinderman, John R. Wetterau, Richard E. Gregg, Daniel J. Rader, David A. Gordon, Bernadette Kienzle, Edward O'Rourke, Sharp Daru Young |
| المصدر: | Journal of Biological Chemistry. 270:14281-14285 |
| بيانات النشر: | Elsevier BV, 1995. |
| سنة النشر: | 1995 |
| مصطلحات موضوعية: | Male, Protein subunit, Molecular Sequence Data, Mutant, Protein Disulfide-Isomerases, Sf9, Biochemistry, Microsomal triglyceride transfer protein, Cell Line, Structure-Activity Relationship, medicine, Humans, Isomerases, Protein disulfide-isomerase, Molecular Biology, Triglycerides, DNA Primers, Glycoproteins, chemistry.chemical_classification, Base Sequence, biology, Endoplasmic reticulum, Abetalipoproteinemia, Cell Biology, Middle Aged, medicine.disease, Molecular biology, Nucleopolyhedroviruses, Cholesterol Ester Transfer Proteins, Amino acid, chemistry, Mutation, biology.protein, Carrier Proteins |
| الوصف: | The microsomal triglyceride transfer protein (MTP) is a heterodimer composed of the multifunctional enzyme, protein disulfide-isomerase, and a unique large, 97 kDa, subunit. It is found as a soluble protein within the lumen of the endoplasmic reticulum of liver and intestine and is required for the assembly of very low density lipoproteins and chylomicrons. Mutations in MTP which result in an absence of MTP function have been shown to cause abetalipoproteinemia. Here, the gene encoding the MTP 97-kDa subunit of an abetalipoproteinemic subject, which we have previously demonstrated lacks MTP activity and protein (Wetterau, J. R., Aggerbeck, L. P., Bouma, M.-E., Eisenberg, C., Munck, A., Hermier, M., Schmitz, J., Gay, G., Rader, D. J., and Gregg, R. E. (1992) Science 258, 999-1001), was isolated and sequenced. A nonsense mutation, which predicts the truncation of the protein by 30 amino acids, was identified. To investigate if this apparently subtle change in MTP could explain the observed absence of MTP, protein disulfide-isomerase was co-expressed with either the normal or mutant MTP 97-kDa subunit in Sf9 insect cells using a baculovirus expression system. Although there were high levels of expression of both the normal and mutant forms of the MTP 97-kDa subunit, only the normal subunit was able to form a stable, soluble complex with protein disulfide-isomerase. These results indicate that the carboxyl-terminal 30 amino acids of the MTP 97-kDa subunit plays an important role in its interaction with protein disulfide-isomerase. |
| تدمد: | 0021-9258 |
| DOI: | 10.1074/jbc.270.24.14281 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5656bd56d013fd200a48a26a76dff789 https://doi.org/10.1074/jbc.270.24.14281 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5656bd56d013fd200a48a26a76dff789 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00219258 |
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| DOI: | 10.1074/jbc.270.24.14281 |