Koch Michael, Camp Simon, Collen Trevor, Avila David, Salomonsen Jan, Wallny Hans-Joachim, van Hateren Andrew, Hunt Lawrence, Jacob Jansen P, Johnston Fiona, Marston Denise A, Shaw Iain, Dunbar P Rod, Cerundolo Vincenzo, Jones E Yvonne, Kaufman Jim
Cancer Research UK Receptor Structure Research Group, The Henry Wellcome Building for Genomic Medicine, Roosevelt Drive, Headington, Oxford OX3 7BN, UK.
Immunity. 2007 Dec;27(6):885-99. doi: 10.1016/j.immuni.2007.11.007.
Little is known about the structure of major histocompatibility complex (MHC) molecules outside of mammals. Only one class I molecule in the chicken MHC is highly expressed, leading to strong genetic associations with infectious pathogens. Here, we report two structures of the MHC class I molecule BF2*2101 from the B21 haplotype, which is known to confer resistance to Marek's disease caused by an oncogenic herpesvirus. The binding groove has an unusually large central cavity, which confers substantial conformational flexibility to the crucial residue Arg9, allowing remodeling of key peptide-binding sites. The coupled variation of anchor residues from the peptide, utilizing a charge-transfer system unprecedented in MHC molecules, allows peptides with conspicuously different sequences to be bound. This promiscuous binding extends our understanding of ways in which MHC class I molecules can present peptides to the immune system and might explain the resistance of the B21 haplotype to Marek's disease.
除哺乳动物外，人们对主要组织相容性复合体（MHC）分子的结构知之甚少。鸡MHC中只有一种I类分子高度表达，导致与传染性病原体有很强的遗传关联。在这里，我们报告了来自B21单倍型的MHC I类分子BF2*2101的两种结构，已知该单倍型可赋予对由致癌疱疹病毒引起的马立克氏病的抗性。结合槽有一个异常大的中央腔，这赋予关键残基Arg9相当大的构象灵活性，允许关键肽结合位点重塑。利用MHC分子中前所未有的电荷转移系统，肽的锚定残基的耦合变异允许结合序列明显不同的肽。这种混杂结合扩展了我们对MHC I类分子向免疫系统呈递肽的方式的理解，并可能解释B21单倍型对马立克氏病的抗性。
