GSBS Student Publications
Title
Noble metals strip peptides from class II MHC proteins
GSBS Program
Biochemistry & Molecular Pharmacology
UMMS Affiliation
Graduate School of Biomedical Sciences; Department of Pathology; Department of Biochemistry and Molecular Pharmacology
Date
3-1-2006
Document Type
Article
Medical Subject Headings
Allosteric Site; Animals; Antigen Presentation; Autoimmune Diseases; CD4-Positive T-Lymphocytes; Chromatography, Gel; Cisplatin; Dose-Response Relationship, Drug; Drosophila melanogaster; Enzyme-Linked Immunosorbent Assay; Gold Sodium Thiomalate; Histocompatibility Antigens Class II; Humans; Kinetics; Major Histocompatibility Complex; Models, Statistical; Molecular Conformation; Peptides; Protein Binding; Sodium Hypochlorite; Time Factors
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.
Rights and Permissions
Citation: Nat Chem Biol. 2006 Apr;2(4):197-201. Epub 2006 Feb 26. Link to article on publisher's site
DOI of Published Version
10.1038/nchembio773
Related Resources
Journal Title
Nature chemical biology
PubMed ID
16505807
Repository Citation
De Wall, Stephen J.; Painter, Corrie A.; Stone, Jennifer D.; Bandaranayake, Rajintha M.; Wiley, Don C.; Mitchison, Timothy J.; Stern, Lawrence J.; and DeDecker, Brian S., "Noble metals strip peptides from class II MHC proteins" (2006). GSBS Student Publications. 265.
https://escholarship.umassmed.edu/gsbs_sp/265