CD28 hinge used in chimeric antigen receptor (CAR) T-cells exhibits local structure and conformational exchange amidst global disorder.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
31 Aug 2024
31 Aug 2024
Historique:
received:
21
06
2024
accepted:
21
08
2024
medline:
1
9
2024
pubmed:
1
9
2024
entrez:
31
8
2024
Statut:
epublish
Résumé
T-cell therapies based on chimeric antigen receptor (CAR) targeting of a tumor-specific antigen offer hope for patients with relapsed or refractory cancers. CAR hinge and transmembrane regions link antigen recognition domains to intracellular signal transduction domains. Here, we apply biophysical methods to characterize the structure and dynamic properties of the CD28 CAR hinge (CD28H) used in an FDA-approved CD19 CAR for the treatment of B-lineage leukemia/lymphoma. By using nuclear Overhauser effect spectroscopy (NOESY), which detects even transiently occupied structural motifs, we observed otherwise elusive local structural elements amidst overall disorder in CD28H, including a conformational switch from a native β-strand to a 3
Identifiants
pubmed: 39217198
doi: 10.1038/s42003-024-06770-w
pii: 10.1038/s42003-024-06770-w
doi:
Substances chimiques
CD28 Antigens
0
Receptors, Chimeric Antigen
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1072Subventions
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : P41GM111135
Informations de copyright
© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
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