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A structural framework for deciphering the link between I-A(g7) and autoimmune diabetes

Academic Article
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Overview

related to degree

  • Scott, Christopher, Ph.D. in Biology, Scripps Research 1993 - 1998

authors

  • Corper, A. L.
  • Stratmann, T.
  • Apostolopoulos, V.
  • Scott, Christopher
  • Garcia, K. C.
  • Kang, A. S.
  • Wilson, Ian
  • Teyton, Luc

publication date

  • April 2000

journal

  • Science  Journal

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.

subject areas

  • Alleles
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Aspartic Acid
  • Crystallography, X-Ray
  • Diabetes Mellitus, Type 1
  • Drosophila melanogaster
  • Genes, MHC Class II
  • Glutamate Decarboxylase
  • Histocompatibility Antigens Class II
  • Humans
  • Hydrogen Bonding
  • Mice
  • Mice, Inbred NOD
  • Models, Molecular
  • Molecular Sequence Data
  • Peptide Library
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Secondary
  • Receptors, Antigen, T-Cell
  • Recombinant Proteins
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Identity

International Standard Serial Number (ISSN)

  • 0036-8075

Digital Object Identifier (DOI)

  • 10.1126/science.288.5465.505

PubMed ID

  • 10775108
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Additional Document Info

start page

  • 505

end page

  • 511

volume

  • 288

issue

  • 5465

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