1uvq

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1uvq, resolution 1.8Å

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CRYSTAL STRUCTURE OF HLA-DQ0602 IN COMPLEX WITH A HYPOCRETIN PEPTIDE

Contents

Overview

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.

Disease

Known diseases associated with this structure: Creutzfeldt-Jakob disease, variant, resistance to OMIM:[604305], Multiple sclerosis, susceptibility to OMIM:[604305], Narcolepsy OMIM:[602358], Porphyria variegata OMIM:[600923]

About this Structure

1UVQ is a Protein complex structure of sequences from Homo sapiens with NAG, ZN, GLY and ACY as ligands. Structure known Active Site: AC1. Full crystallographic information is available from OCA.

Reference

Crystal structure of HLA-DQ0602 that protects against type 1 diabetes and confers strong susceptibility to narcolepsy., Siebold C, Hansen BE, Wyer JR, Harlos K, Esnouf RE, Svejgaard A, Bell JI, Strominger JL, Jones EY, Fugger L, Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):1999-2004. Epub 2004 Feb 9. PMID:14769912

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