Atomistic structure and dynamics of the human MHC-I peptide-loading complex
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- Olivier Fisette
- Theoretical Chemistry, Ruhr University Bochum, D-44780 Bochum, Germany;
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- Gunnar F. Schröder
- Institute of Biological Information Processing (IBI-7: Structural Biochemistry), Forschungszentrum Jülich, D-52425 Jülich, Germany;
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- Lars V. Schäfer
- Theoretical Chemistry, Ruhr University Bochum, D-44780 Bochum, Germany;
抄録
<jats:title>Significance</jats:title> <jats:p>The major histocompatibility complex class-I (MHC-I) peptide-loading complex (PLC) translocates cytosolic degradation products to the endoplasmic reticulum to load antigenic peptides onto MHC-I molecules. Stable peptide–MHC-I complexes are presented at the cell surface to mirror cellular contents for patrolling T cells, which protect against viral infections and cancer-causing mutations by inducing apoptosis in cells that expose nonself peptides. Due to its size and dynamic nature, the atomic-level details of the PLC remained unknown. We built an all-atom model of the human MHC-I PLC by combining the recent 9.9-Å resolution cryo-EM density with microsecond molecular dynamics simulations in a membrane and water environment (1.6 million atoms). The results provide unprecedented insights into the molecular underpinnings of our adaptive immune response.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 117 (34), 20597-20606, 2020-08-11
Proceedings of the National Academy of Sciences