Download MendeleyA structural framework for deciphering the link between I-Ag7 and autoimmune diabetes.
Corper, A.L., Stratmann, T., Apostolopoulos, V., Scott, C.A., Garcia, K.C., Kang, A.S., Wilson, I.A., Teyton, L.(2000) Science 288: 505-511
- PubMed: 10775108
- DOI: https://doi.org/10.1126/science.288.5465.505
- Primary Citation of Related Structures:
1ES0 - PubMed Abstract:
Susceptibility to murine and human insulin-dependent diabetes mellitus correlates strongly with major histocompatibility complex (MHC) class II I-A or HLA-DQ alleles that lack an aspartic acid at position beta57. I-Ag7 lacks this aspartate and is the only class II allele expressed by the nonobese diabetic mouse. The crystal structure of I-Ag7 was determined at 2.6 angstrom resolution as a complex with a high-affinity peptide from the autoantigen glutamic acid decarboxylase (GAD) 65. I-Ag7 has a substantially wider peptide-binding groove around beta57, which accounts for distinct peptide preferences compared with other MHC class II alleles. Loss of Asp(beta57) leads to an oxyanion hole in I-Ag7 that can be filled by peptide carboxyl residues or, perhaps, through interaction with the T cell receptor.
Organizational Affiliation:
Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
