Dipeptides promote folding and peptide binding of MHC class I molecules

Dipeptides promote folding and peptide binding of MHC class I molecules
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DOI:
10.1073/pnas.1308672110
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发表时间:
2013-09
期刊:
Proceedings of the National Academy of Sciences
影响因子:
--
通讯作者:
S. Saini;Katja Ostermeir;V. Ramnarayan;H. Schuster;M. Zacharias;S. Springer
S. Saini;Katja Ostermeir;V. Ramnarayan;H. Schuster;M. Zacharias;S. Springer
中科院分区:
其他
文献类型:
--
作者:
S. Saini;Katja Ostermeir;V. Ramnarayan;H. Schuster;M. Zacharias;S. Springer

文献摘要

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MHC I类分子仅以符合严格长度和序列要求的高亲和力结合那些肽。我们现在已经研究了哪些肽可以帮助I类分子的体外折叠,并且我们发现二肽甘氨酰-亮氨酸有效地支持HLA-A*02:01和H-2Kb折叠成快速结合高亲和力肽的肽受体构象。用甘氨酰-亮氨酸处理细胞诱导肽受体H-2Kb和HLA-A*02:01在细胞表面的积累。具有疏水性第二氨基酸的其他二肽显示类似的增强作用。我们的数据表明,二肽结合到F口袋一样的C-末端氨基酸的高亲和力肽。
MHC class I molecules bind only those peptides with high affinity that conform to stringent length and sequence requirements. We have now investigated which peptides can aid the in vitro folding of class I molecules, and we find that the dipeptide glycyl-leucine efficiently supports the folding of HLA-A*02:01 and H-2Kb into a peptide-receptive conformation that rapidly binds high-affinity peptides. Treatment of cells with glycyl-leucine induces accumulation of peptide-receptive H-2Kb and HLA-A*02:01 at the surface of cells. Other dipeptides with a hydrophobic second amino acid show similar enhancement effects. Our data suggest that the dipeptides bind into the F pocket like the C-terminal amino acids of a high-affinity peptide.