Successive crystal structure snapshots suggest the basis for MHC class I peptide loading and editing by tapasin
| Autor: | Sara Pellegrino, Xiao Han, I. Hafstrand, Linda Janssen, Anca Apavaloaei, Sebastian Springer, Adil Doganay Duru, Johan Nilvebrant, Renee Potens, Ece Canan Sayitoglu, Tatyana Sandalova, Benjamin J. Josey, Adnane Achour, Anna-Maria Georgoudaki, Renhua Sun, Per-Åke Nygren, Didem Ozkazanc |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Models Molecular Peptide binding Peptide chemical and pharmacologic phenomena Major histocompatibility complex Crystallography X-Ray Epitope Protein Structure Secondary 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Tapasin Leucine MHC class I Animals Humans chemistry.chemical_classification Mice Knockout Multidisciplinary Dipeptide biology Antigen processing Histocompatibility Antigens Class I Membrane Transport Proteins Biological Sciences Cell biology 030104 developmental biology HEK293 Cells chemistry 030220 oncology & carcinogenesis Mutation biology.protein Protein Binding |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 116(11) |
| ISSN: | 1091-6490 |
| Popis: | MHC-I epitope presentation to CD8 + T cells is directly dependent on peptide loading and selection during antigen processing. However, the exact molecular bases underlying peptide selection and binding by MHC-I remain largely unknown. Within the peptide-loading complex, the peptide editor tapasin is key to the selection of MHC-I–bound peptides. Here, we have determined an ensemble of crystal structures of MHC-I in complex with the peptide exchange-associated dipeptide GL, as well as the tapasin-associated scoop loop, alone or in combination with candidate epitopes. These results combined with mutation analyses allow us to propose a molecular model underlying MHC-I peptide selection by tapasin. The N termini of bound peptides most probably bind first in the N-terminal and middle region of the MHC-I peptide binding cleft, upon which the peptide C termini are tested for their capacity to dislodge the tapasin scoop loop from the F pocket of the MHC-I cleft. Our results also indicate important differences in peptide selection between different MHC-I alleles. |
| Databáze: | OpenAIRE |
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