MHC-II dynamics are maintained in HLA-DR allotypes to ensure catalyzed peptide exchange

Simple item page
dc.citation.firstpage1196
dc.citation.issueNumber10
dc.citation.journalTitleNature Chemical Biology
dc.citation.lastpage1204
dc.citation.volumeNumber19
dc.contributor.authorAbualrous, Esam T.
dc.contributor.authorStolzenberg, Sebastian
dc.contributor.authorSticht, Jana
dc.contributor.authorWieczorek, Marek
dc.contributor.authorRoske, Yvette
dc.contributor.authorGünther, Matthias
dc.contributor.authorDähn, Steffen
dc.contributor.authorBoesen, Benedikt B.
dc.contributor.authorCalvo, Marcos Martínez
dc.contributor.authorBiese, Charlotte
dc.contributor.authorKuppler, Frank
dc.contributor.authorMedina-García, Álvaro
dc.contributor.authorÁlvaro-Benito, Miguel
dc.contributor.authorHöfer, Thomas
dc.contributor.authorNoé, Frank
dc.contributor.authorFreund, Christian
dc.date.accessioned2024-05-03T15:51:19Z
dc.date.available2024-05-03T15:51:19Z
dc.date.issued2023
dc.description.abstractPresentation of antigenic peptides by major histocompatibility complex class II (MHC-II) proteins determines T helper cell reactivity. The MHC-II genetic locus displays a large degree of allelic polymorphism influencing the peptide repertoire presented by the resulting MHC-II protein allotypes. During antigen processing, the human leukocyte antigen (HLA) molecule HLA-DM (DM) encounters these distinct allotypes and catalyzes exchange of the placeholder peptide CLIP by exploiting dynamic features of MHC-II. Here, we investigate 12 highly abundant CLIP-bound HLA-DRB1 allotypes and correlate dynamics to catalysis by DM. Despite large differences in thermodynamic stability, peptide exchange rates fall into a target range that maintains DM responsiveness. A DM-susceptible conformation is conserved in MHC-II molecules, and allosteric coupling between polymorphic sites affects dynamic states that influence DM catalysis. As exemplified for rheumatoid arthritis, we postulate that intrinsic dynamic features of peptide–MHC-II complexes contribute to the association of individual MHC-II allotypes with autoimmune disease.
dc.identifier.citationAbualrous, E. T., Stolzenberg, S., Sticht, J., Wieczorek, M., Roske, Y., Günther, M., Dähn, S., Boesen, B. B., Calvo, M. M., Biese, C., Kuppler, F., Medina-García, Á., Álvaro-Benito, M., Höfer, T., Noé, F., & Freund, C. (2023). MHC-II dynamics are maintained in HLA-DR allotypes to ensure catalyzed peptide exchange. Nature Chemical Biology, 19(10), 1196–1204. https://doi.org/10.1038/s41589-023-01316-3
dc.identifier.digitals41589-023-01316-3
dc.identifier.doihttps://doi.org/10.1038/s41589-023-01316-3
dc.identifier.urihttps://hdl.handle.net/1911/115620
dc.language.isoeng
dc.publisherSpringer Nature
dc.rightsExcept where otherwise noted, this work is licensed under a Creative Commons Attribution (CC BY) license. Permission to reuse, publish, or reproduce the work beyond the terms of the license or beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleMHC-II dynamics are maintained in HLA-DR allotypes to ensure catalyzed peptide exchange
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
s41589-023-01316-3.pdf
Size:
7.65 MB
Format:
Adobe Portable Document Format
Download
Collections
Faculty Publications
Chemistry Publications