Human herpesvirus 7 U21 tetramerizes to associate with class I major histocompatibility complex molecules.
Human herpesvirus 7 U21 tetramerizes to associate with class I major histocompatibility complex molecules.
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人类疱疹病毒 7 U21 四聚化，与 I 类主要组织相容性复合体分子结合。
DOI：
10.1128/jvi.02639-13
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发表时间：
2014
影响因子：
5.4
通讯作者：
Hudson,AmyW
中科院分区：
文献类型：
--
作者：
May,NathanA;Wang,Qiuhong;Balbo,Andrea;Konrad,SherylL;Buchli,Rico;Hildebrand,WilliamH;Schuck,Peter;Hudson,AmyW
来自人类疱疹病毒7的U21基因产物结合并将I类主要组织相容性复合体（MHC）分子重定向到溶酶体腔室。U21将I类MHC分子转移到溶酶体的分子机制尚不清楚。在这里，我们重建了纯化的可溶性U21和I类MHC分子之间的相互作用，表明U21不需要额外的细胞蛋白来与I类MHC分子相互作用。我们的研究结果表明，U21本身预计含有MHC I类蛋白折叠，与I类MHC分子作为四聚体紧密相互作用，以4:2的化学计量。这些观察结果有助于阐明一个精细的模型，该模型描述了U21将I类MHC分子护送到溶酶体室的机制。在本报告中，我们发现人类疱疹病毒7 （HHV-7）免疫逃避蛋白U21本身是一类MHC样蛋白，它以四聚体的形式与一类MHC分子高亲和力结合，并将它们护送到溶酶体中，在那里它们被降解。虽然许多I类MHC样分子已经被详细描述过，但这种不寻常的病毒I类蛋白的功能是四聚体，与I类MHC分子以4:2的比例结合，阐明了I类MHC样蛋白同质寡聚化的功能意义。
The U21 gene product from human herpesvirus 7 binds to and redirects class I major histocompatibility complex (MHC) molecules to a lysosomal compartment. The molecular mechanism by which U21 reroutes class I MHC molecules to lysosomes is not known. Here, we have reconstituted the interaction between purified soluble U21 and class I MHC molecules, suggesting that U21 does not require additional cellular proteins to interact with class I MHC molecules. Our results demonstrate that U21, itself predicted to contain an MHC class I-like protein fold, interacts tightly with class I MHC molecules as a tetramer, in a 4:2 stoichiometry. These observations have helped to elucidate a refined model describing the mechanism by which U21 escorts class I MHC molecules to the lysosomal compartment.IMPORTANCEIn this report, we show that the human herpesvirus 7 (HHV-7) immunoevasin U21, itself a class I MHC-like protein, binds with high affinity to class I MHC molecules as a tetramer and escorts them to lysosomes, where they are degraded. While many class I MHC-like molecules have been described in detail, this unusual viral class I-like protein functions as a tetramer, associating with class I MHC molecules in a 4:2 ratio, illuminating a functional significance of homooligomerization of a class I MHC-like protein.