Nonstandard peptide binding revealed by crystal structures of HLA-B*5101 complexed with HIV immunodominant epitopes
Nonstandard peptide binding revealed by crystal structures of HLA-B*5101 complexed with HIV immunodominant epitopes
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DOI：
10.4049/jimmunol.165.6.3260
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发表时间：
2000-09-15
影响因子：
4.4
通讯作者：
Jones, EY
中科院分区：
文献类型：
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作者：
Maenaka, K;Maenaka, T;Jones, EY
通过X射线晶体学测定了与来自HIV-1的免疫显性肽表位8聚体TAFTIPSI和9聚体LPPVVAKEI复合的人MHC I类等位基因HLA-B*5101的晶体结构。在这两种复合物中，N-末端锚（P1）口袋中的氢键网络由于171位的标准酪氨酸被组氨酸取代而重排，这导致肽N末端的非标准定位，其被B*5101限制性T细胞克隆识别。出乎意料的是，P5肽残基似乎起着锚的作用，将肽异常深入地拉入B51的肽结合沟中。P1和P5的独特特性可能是9-mer肽的锯齿形构象和B*5101的缓慢组装的原因。B51和其他MHC I类等位基因的α 1-螺旋C-末端区域的表面特征的比较突出了主要的静电差异，这可能是重要的，在确定人类杀伤细胞Ig样受体结合的特异性。
The crystal structures of the human MHC class I allele HLA-B*5101 in complex with 8-mer, TAFTIPSI, and 9-mer, LPPVVAKEI, immunodominant peptide epitopes from HIV-1 have been determined by x-ray crystallography, In both complexes, the hydrogen-bonding network in the N-terminal anchor (P1) pocket is rearranged as a result of the replacement of the standard tyrosine with histidine at position 171, This results in a nonstandard positioning of the peptide N terminus, which is recognized by B*5101-restricted T cell clones. Unexpectedly, the P5 peptide residues appear to act as anchors, drawing the peptides unusually deeply into the peptide-binding groove of B51. The unique characteristics of P1 and P5 are likely to be responsible for the zig-zag conformation of the 9-mer peptide and the slow assembly of B*5101. A comparison of the surface characteristics in the alpha1-helix C-terminal region for B51 and other MHC class I alleles highlights mainly electrostatic differences that may be important in determining the specificity of human killer cell Ig-like receptor binding.