ABC Transporters and Immunity: Mechanism of Self-Defense
ABC Transporters and Immunity: Mechanism of Self-Defense
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DOI：
10.1021/bi300128f
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发表时间：
2012-06-26
期刊：
影响因子：
2.9
通讯作者：
Tampe, Robert
中科院分区：
文献类型：
--
作者：
Hinz, Andreas;Tampe, Robert
与抗原加工相关的转运体（TAP）是一种不对称ATP结合盒（ABC）转运体的原型，它利用ATP结合和水解将肽从细胞质溶胶转运到内质网（ER）的管腔。在这里，我们回顾了肽结合、ATP结合和水解的分子细节，以及核苷酸结合结构域和驱动溶质跨内质膜易位的跨膜结构域之间的变构串扰。我们还讨论了ABC转运蛋白的一般分子结构，并证明了结构和功能研究对于更好地理解非对称ABC转运蛋白非规范位点的作用的重要性。肽结合和特异性的几个方面说明了肽易位的细节。此外，这种ABC转运蛋白构成了主要组织相容性复合体I类（MHC I）肽装载机制的中心部分。因此，TAP面临着许多病毒因子，这些病毒因子可以阻止病毒感染细胞中的抗原易位和MHC I装载。我们回顾了这些病毒因子如何被用作分子工具来破译溶质易位的机制方面，并讨论了它们如何有助于TAP的结构分析。
The transporter associated with antigen processing (TAP) is a prototype of an asymmetric ATP-binding cassette (ABC) transporter, which uses ATP binding and hydrolysis to translocate peptides from the cytosol to the lumen of the endoplasmic reticulum (ER). Here, we review molecular details of peptide binding and ATP binding and hydrolysis as well as the resulting allosteric cross-talk between the nucleotide-binding domains and the transmembrane domains that drive translocation of the solute across the ER membrane. We also discuss the general molecular architecture of ABC transporters and demonstrate the importance of structural and functional studies for a better understanding of the role of the noncanonical site of asymmetric ABC transporters. Several aspects of peptide binding and specificity illustrate details of peptide translocation by TAP. Furthermore, this ABC transporter forms the central part of the major histocompatibility complex class I (MHC I) peptide-loading machinery. Hence, TAP is confronted with a number of viral factors, which prevent antigen translocation and MHC I loading in virally infected cells. We review how these viral factors have been used as molecular tools to decipher mechanistic aspects of solute translocation and discuss how they can help in the structural analysis of TAP.