The structure and stability of an HLA-A*0201/octameric tax peptide complex with an empty conserved peptide-N-terminal binding site
The structure and stability of an HLA-A*0201/octameric tax peptide complex with an empty conserved peptide-N-terminal binding site
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DOI：
10.4049/jimmunol.164.12.6398
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发表时间：
2000-06-15
影响因子：
4.4
通讯作者：
Wiley, DC
中科院分区：
文献类型：
--
作者：
Khan, AR;Baker, BM;Wiley, DC
测定了人类T细胞淋巴营养病毒-1(HTLV-1)的八聚体多肽Tax8(LFGYPVYV)与人类I类MHC分子人类白细胞抗原A2(HLAA2)的晶体结构。该结构与新提纯的、更高分辨率的(1.8 Angstrom)结构相比较，该结构与具有多一个N-末端残基的非单体Tax9肽(LLFGYPVYV)形成络合物，尽管在Tax8/HLA-A2复合体的保守的N-端肽结合口袋中没有结合的肽残基(P1)，但两种复合体的结构基本相同。Tax8复合体中的水分子取代了Tax9肽的末端氨基，并在肽结合槽末端的二级结构元件之间调节了氢键网络。热变性测量表明，Tax8复合体的稳定性比Tax9复合体差得多，Delta T-m=16℃，但两者都能敏化靶细胞，使HTLV-1感染者的一些税收特异性CTL裂解。因此，PI多肽残基的缺乏不足以阻止多肽结合部位的“封闭构象”的形成，TCR亲和力测量和细胞毒性T细胞分析表明，Tax8/HLA-A2复合体在功能上不与Tax9/HLA-A2复合体特异的A6-TCR承载T细胞克隆发生交叉反应。
The crystal structure of the human class I MHC molecule HLA-A2 complexed with of an octameric peptide, Tax8 (LFGYPVYV), from human T cell lymphotrophic virus-1 (HTLV-1) has been determined. This structure is compared with a newly refined, higher resolution (1.8 Angstrom) structure of HLA-A2 complexed with the nonameric Tax9 peptide (LLFGYPVYV) with one more N-terminal residue, Despite the absence of a peptide residue (P1) bound in the conserved N-terminal peptide-binding pocket of the Tax8/HLA-A2 complex, the structures of the two complexes are essentially identical. Water molecules in the Tax8 complex replace the terminal amino group of the Tax9 peptide and mediate a network of hydrogen bonds among the secondary structural elements at that end of the peptide-binding groove. Thermal denaturation measurements indicate that the Tax8 complex is much less stable, Delta T-m = 16 degrees C, than the Tax9 complex, but both can sensitize target cells for lysis by some Tax-specific CTL from HTLV-1 infected individuals. The absence of a Pi peptide residue is thus not enough to prevent formation of a "closed conformation" of the peptide-binding site, TCR affinity measurements and cytotoxic T cell assays indicate that the Tax8/HLA-A2 complex does not functionally cross-react with the A6-TCR-bearing T cell clone specific for Tax9/HLA-A2 complexes.