Analysis of interactions in a tapasin/class I complex provides a mechanism for peptide selection
Analysis of interactions in a tapasin/class I complex provides a mechanism for peptide selection
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DOI：
10.1038/sj.emboj.7601624
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发表时间：
2007-03-21
期刊：
影响因子：
11.4
通讯作者：
Bouvier, Marlene
中科院分区：
文献类型：
--
作者：
Chen, Mingnan;Bouvier, Marlene
我们研究了可溶性TPN/HLA-B*0801复合体中的相互作用，以获得对TPN功能的机械性见解。结果表明，TPN通过增加溶液中活性/非活性多肽缺陷型HLA-B*0801分子的比例而发挥伴侣作用。TPN通过拓宽HLA-B*0801分子的结合槽，使多肽结合和解离更快。我们的数据表明，TPN辅助的多肽选择机制依赖于凹槽C末端保守氢键的破坏。沿着整个沟槽长度的肽序列依赖的相互作用也在这一机制中发挥作用。我们认为，TPN通过一个复杂的机械过程影响抗原肽的呈递，在这个过程中，不能从I类分子上构象解离TPN的结合候选肽被排除在谱系之外。总体而言，这些研究统一了我们对TPN功能的理解。
We examined interactions in a soluble tapasin (TPN)/HLA-B* 0801 complex to gain mechanistic insights into the functions of TPN. Results show that TPN acts as a chaperone by increasing the ratio of active-to-inactive peptide-deficient HLA-B*0801 molecules in solution. TPN causes peptides to associate and dissociate faster owing to its effect on widening the binding groove of HLA-B*0801 molecules. Our data indicate that a TPN-assisted mechanism of peptide selection relies on disruption of conserved hydrogen bonds at the C-terminal end of the groove. Peptide sequence-dependent interactions along the entire length of the groove also play a role in this mechanism. We suggest that TPN influences presentation of antigenic peptides according to a mechanistically complicated process in which bound candidate peptides that are unable to conformationally disengage TPN from class I molecules are excluded from the repertoire. Overall, these studies unify our understanding of the functions of TPN.