Two distinct proteolytic processes in the generation of a major histocompatibility complex class I-presented peptide
| Autor: | Abie Craiu, Kenneth L. Rock, Tatos Akopian, Alfred L. Goldberg |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Proteasome Endopeptidase Complex
Guinea Pigs Lactacystin Peptide Biology Endoplasmic Reticulum Major histocompatibility complex Epitopes Interferon-gamma chemistry.chemical_compound Multienzyme Complexes MHC class I Tumor Cells Cultured Animals chemistry.chemical_classification Multidisciplinary Hydrolysis C-terminus Endoplasmic reticulum Histocompatibility Antigens Class I Biological Sciences N-terminus Cysteine Endopeptidases chemistry Proteasome Biochemistry biology.protein Oligopeptides |
| Zdroj: | Proceedings of the National Academy of Sciences. 94:10850-10855 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.94.20.10850 |
| Popis: | Although cellular proteins degraded by proteasomes are the source of most antigenic peptides presented on major histocompatibility complex class I molecules, it is unknown whether the eight- to nine-residue peptides that fit in the binding groove of class I molecules are directly produced by proteasomes alonein vivo. If the eight-residue peptide SIINFEKL from chicken ovalbumin is extended by one or several residues at its C terminus and microinjected into cells or expressed from a minigene, it is processed and presented on major histocompatibility complex class I. However, processing and presentation are inhibited by proteasome inhibitors, such as lactacystin. In contrast, when SIINFEKL is extended by 2 to 25 residues at its N terminus, its presentation is not blocked by proteasome inhibitors. N-terminal processing also can occur when the extended peptide is cotranslationally inserted into the endoplasmic reticulum. Thus, two different proteolytic steps in the generation of an chicken ovalbumin-presented peptide can be distinguished. Cleavage by the proteasome defines the proper C terminus, whereas distinct peptidase(s) in the cytosol or endoplasmic reticulum may generate the appropriate N terminus from extended peptides. |
| Databáze: | OpenAIRE |
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