Kumar Pravin, Vahedi-Faridi Ardeschir, Merino Elena, López de Castro José A, Volz Armin, Ziegler Andreas, Saenger Wolfram, Uchanska-Ziegler Barbara
Institut für Immungenetik, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Thielallee 73, 14195 Berlin, Germany.
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2007 Jul 1;63(Pt 7):631-4. doi: 10.1107/S1744309107029077. Epub 2007 Jun 29.
The product of the human major histocompatibility (HLA) class I allele HLA-B1402 only differs from that of allele HLA-B1403 at amino-acid position 156 of the heavy chain (Leu in HLA-B1402 and Arg in HLA-B1403). However, both subtypes are known to be differentially associated with the inflammatory rheumatic disease ankylosing spondylitis (AS) in black populations in Cameroon and Togo. HLA-B1402 is not associated with AS, in contrast to HLA-B1403, which is associated with this disease in the Togolese population. The products of these alleles can present peptides with Arg at position 2, a feature shared by a small group of other HLA-B antigens, including HLA-B2705, the prototypical AS-associated subtype. Complexes of HLA-B1402 with a viral peptide (RRRWRRLTV, termed pLMP2) and a self-peptide (IRAAPPPLF, termed pCatA) were prepared and were crystallized using polyethylene glycol as precipitant. The complexes crystallized in space groups P2(1) (pLMP2) and P2(1)2(1)2(1) (pCatA) and diffracted synchrotron radiation to 2.55 and 1.86 A resolution, respectively. Unambiguous solutions for both data sets were obtained by molecular replacement using a peptide-complexed HLA-B*2705 molecule (PDB code 1jge) as a search model.
人类主要组织相容性复合体(HLA)I类等位基因HLA - B1402的产物与等位基因HLA - B1403的产物仅在重链的氨基酸位置156处存在差异(HLA - B1402中为亮氨酸,HLA - B1403中为精氨酸)。然而,已知这两种亚型在喀麦隆和多哥的黑人人群中与炎性风湿性疾病强直性脊柱炎(AS)存在不同关联。与HLA - B1403不同,HLA - B1402与AS无关联,HLA - B1403在多哥人群中与该疾病相关。这些等位基因的产物能够呈递在第2位带有精氨酸的肽段,这是包括HLA - B2705(AS相关原型亚型)在内的一小部分其他HLA - B抗原所共有的特征。制备了HLA - B1402与病毒肽(RRRWRRLTV,称为pLMP2)和自身肽(IRAAPPPLF,称为pCatA)的复合物,并使用聚乙二醇作为沉淀剂使其结晶。这些复合物分别在空间群P2(1)(pLMP2)和P2(1)2(1)2(1)(pCatA)中结晶,并分别将同步辐射衍射至2.55 Å和1.86 Å的分辨率。通过使用肽复合的HLA - B2705分子(PDB代码1jge)作为搜索模型进行分子置换,获得了两个数据集的明确解决方案。