Crystal structure of HLA-DQ0602 that protects against type 1 diabetes and confers strong susceptibility to narcolepsy
Crystal structure of HLA-DQ0602 that protects against type 1 diabetes and confers strong susceptibility to narcolepsy
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DOI：
10.1073/pnas.0308458100
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发表时间：
2004-02-17
影响因子：
11.1
通讯作者：
Fugger, L
中科院分区：
文献类型：
--
作者：
Siebold, C;Hansen, BE;Fugger, L
MHC II类分子DQ 0602赋予对发作性睡病的强烈易感性，但对1型糖尿病的主要保护。DQ0602的晶体结构揭示了这些对比遗传特性背后的分子特征。与具有不同疾病关联的同源DQ分子的结构比较突出了P6口袋的体积和P9口袋的特异性之间的先前未被认识到的相互作用，这意味着呈现扩展的肽库对于针对1型糖尿病的显性保护至关重要。在嗜睡症中，P4口袋的体积似乎是易感性的中心，这表明特定肽群的呈现起着重要作用。
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.