Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

The MHC class II molecule DQ0602 confers strong susceptibility to narcolepsy but dominant protection against type 1 diabetes. The crystal structure of DQ0602 reveals the molecular features underlying these contrasting genetic properties. Structural comparisons to homologous DQ molecules with differential disease associations highlight a previously unrecognized interplay between the volume of the P6 pocket and the specificity of the P9 pocket, which implies that presentation of an expanded peptide repertoire is critical for dominant protection against type 1 diabetes. In narcolepsy, the volume of the P4 pocket appears central to the susceptibility, suggesting that the presentation of a specific peptide population plays a major role.

Original publication

DOI

10.1073/pnas.0308458100

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

17/02/2004

Volume

101

Pages

1999 - 2004

Keywords

Alleles, Amino Acid Sequence, Binding Sites, Crystallography, X-Ray, Diabetes Mellitus, Type 1, Genetic Predisposition to Disease, HLA-DQ Antigens, HLA-DQ beta-Chains, Humans, Membrane Glycoproteins, Models, Molecular, Narcolepsy, Polymorphism, Genetic, Protein Binding, Protein Conformation, Structure-Activity Relationship