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Title: Crystal structure of a TAPBPR–MHC I complex reveals the mechanism of peptide editing in antigen presentation

Abstract

Central to CD8+ T cell–mediated immunity is the recognition of peptide–major histocompatibility complex class I (p–MHC I) proteins displayed by antigen-presenting cells. Chaperone-mediated loading of high-affinity peptides onto MHC I is a key step in the MHC I antigen presentation pathway. However, the structure of MHC I with a chaperone that facilitates peptide loading has not been determined. We report the crystal structure of MHC I in complex with the peptide editor TAPBPR (TAP-binding protein–related), a tapasin homolog. TAPBPR remodels the peptide-binding groove of MHC I, resulting in the release of low-affinity peptide. Changes include groove relaxation, modifications of key binding pockets, and domain adjustments. This structure captures a peptide-receptive state of MHC I and provides insights into the mechanism of peptide editing by TAPBPR and, by analogy, tapasin.


Citation Formats

Jiang, Jiansheng, Natarajan, Kannan, Boyd, Lisa F., Morozov, Giora I., Mage, Michael G., and Margulies, David H. Crystal structure of a TAPBPR–MHC I complex reveals the mechanism of peptide editing in antigen presentation. United States: N. p., 2017. Web. doi:10.1126/science.aao5154.
Jiang, Jiansheng, Natarajan, Kannan, Boyd, Lisa F., Morozov, Giora I., Mage, Michael G., & Margulies, David H. Crystal structure of a TAPBPR–MHC I complex reveals the mechanism of peptide editing in antigen presentation. United States. doi:10.1126/science.aao5154.
Jiang, Jiansheng, Natarajan, Kannan, Boyd, Lisa F., Morozov, Giora I., Mage, Michael G., and Margulies, David H. Thu . "Crystal structure of a TAPBPR–MHC I complex reveals the mechanism of peptide editing in antigen presentation". United States. doi:10.1126/science.aao5154.
@article{osti_1413322,
title = {Crystal structure of a TAPBPR–MHC I complex reveals the mechanism of peptide editing in antigen presentation},
author = {Jiang, Jiansheng and Natarajan, Kannan and Boyd, Lisa F. and Morozov, Giora I. and Mage, Michael G. and Margulies, David H.},
abstractNote = {Central to CD8+ T cell–mediated immunity is the recognition of peptide–major histocompatibility complex class I (p–MHC I) proteins displayed by antigen-presenting cells. Chaperone-mediated loading of high-affinity peptides onto MHC I is a key step in the MHC I antigen presentation pathway. However, the structure of MHC I with a chaperone that facilitates peptide loading has not been determined. We report the crystal structure of MHC I in complex with the peptide editor TAPBPR (TAP-binding protein–related), a tapasin homolog. TAPBPR remodels the peptide-binding groove of MHC I, resulting in the release of low-affinity peptide. Changes include groove relaxation, modifications of key binding pockets, and domain adjustments. This structure captures a peptide-receptive state of MHC I and provides insights into the mechanism of peptide editing by TAPBPR and, by analogy, tapasin.},
doi = {10.1126/science.aao5154},
journal = {Science},
issn = {0036-8075},
number = 6366,
volume = 358,
place = {United States},
year = {2017},
month = {10}
}

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