dc.contributor.author
Abualrous, Esam T.
dc.contributor.author
Stolzenberg, Sebastian
dc.contributor.author
Sticht, Jana
dc.contributor.author
Wieczorek, Marek
dc.contributor.author
Roske, Yvette
dc.contributor.author
Günther, Matthias
dc.contributor.author
Dähn, Steffen
dc.contributor.author
Boesen, Benedikt B.
dc.contributor.author
Martínez Calvo, Marcos
dc.contributor.author
Biese, Charlotte
dc.contributor.author
Kuppler, Frank
dc.contributor.author
Medina-García, Álvaro
dc.contributor.author
Álvaro-Benito, Miguel
dc.contributor.author
Höfer, Thomas
dc.contributor.author
Noé, Frank
dc.contributor.author
Freund, Christian
dc.date.accessioned
2023-10-09T06:38:22Z
dc.date.available
2023-10-09T06:38:22Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/39384
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-39101
dc.description.abstract
Presentation 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.
en
dc.format.extent
25 Seiten
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
Enzyme mechanisms
en
dc.subject
NMR spectroscopy
en
dc.subject.ddc
500 Naturwissenschaften und Mathematik::540 Chemie::540 Chemie und zugeordnete Wissenschaften
dc.title
MHC-II dynamics are maintained in HLA-DR allotypes to ensure catalyzed peptide exchange
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.doi
10.1038/s41589-023-01316-3
dcterms.bibliographicCitation.journaltitle
Nature Chemical Biology
dcterms.bibliographicCitation.number
10
dcterms.bibliographicCitation.pagestart
1196
dcterms.bibliographicCitation.pageend
1204
dcterms.bibliographicCitation.volume
19
dcterms.bibliographicCitation.url
https://doi.org/10.1038/s41589-023-01316-3
refubium.affiliation
Biologie, Chemie, Pharmazie
refubium.affiliation
Mathematik und Informatik
refubium.affiliation.other
Institut für Chemie und Biochemie
refubium.affiliation.other
Institut für Mathematik
refubium.funding
Springer Nature DEAL
refubium.note.author
Die Publikation wurde aus Open Access Publikationsgeldern der Freien Universität Berlin gefördert.
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.isPartOf.issn
1552-4450
dcterms.isPartOf.eissn
1552-4469