Title
Noble metals strip peptides from class II MHC proteins
UMMS Affiliation
Graduate School of Biomedical Sciences; Department of Pathology; Department of Biochemistry and Molecular Pharmacology
Publication Date
2006-03-01
Document Type
Article
Disciplines
Life Sciences | Medicine and Health Sciences
Abstract
Class II major histocompatibility complex (MHC) proteins are essential for normal immune system function but also drive many autoimmune responses. They bind peptide antigens in endosomes and present them on the cell surface for recognition by CD4(+) T cells. A small molecule could potentially block an autoimmune response by disrupting MHC-peptide interactions, but this has proven difficult because peptides bind tightly and dissociate slowly from MHC proteins. Using a high-throughput screening assay we discovered a class of noble metal complexes that strip peptides from human class II MHC proteins by an allosteric mechanism. Biochemical experiments indicate the metal-bound MHC protein adopts a 'peptide-empty' conformation that resembles the transition state of peptide loading. Furthermore, these metal inhibitors block the ability of antigen-presenting cells to activate T cells. This previously unknown allosteric mechanism may help resolve how gold(I) drugs affect the progress of rheumatoid arthritis and may provide a basis for developing a new class of anti-autoimmune drugs.
DOI of Published Version
10.1038/nchembio773
Source
Nat Chem Biol. 2006 Apr;2(4):197-201. Epub 2006 Feb 26. Link to article on publisher's site
Journal/Book/Conference Title
Nature chemical biology
Related Resources
PubMed ID
16505807
Repository Citation
De Wall SJ, Painter CA, Stone JD, Bandaranayake RM, Wiley DC, Mitchison TJ, Stern LJ, DeDecker BS. (2006). Noble metals strip peptides from class II MHC proteins. GSBS Student Publications. https://doi.org/10.1038/nchembio773. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/265