A PROTEASOME-RELATED GENE BETWEEN THE 2 ABC TRANSPORTER LOCI IN THE CLASS-II REGION OF THE HUMAN MHC

A PROTEASOME-RELATED GENE BETWEEN THE 2 ABC TRANSPORTER LOCI IN THE CLASS-II REGION OF THE HUMAN MHC
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DOI:
10.1038/353357a0
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发表时间:
1991-09-26
期刊:
影响因子:
64.8
通讯作者:
TROWSDALE, J
TROWSDALE, J
中科院分区:
综合性期刊1区
文献类型:
--
作者:
GLYNNE, R;POWIS, SH;TROWSDALE, J

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现在可以详细描述免疫系统如何处理细胞质蛋白1-7。 它们在细胞质中明显降解为肽。 然后这些被运输到内质网,在那里它们遇到I类主要组织相容性复合体(MHC)分子。 一旦装载肽,HLA分子通过高尔基体移动到细胞膜。 直到最近,还没有确定没有信号序列的肽如何穿过ER膜。 然而,许多论文现在已经描述了ABC(ATP结合盒)超家族的一对膜转运蛋白基因,其是该功能的有吸引力的候选者8-12。 这两个转运蛋白基因都位于MHC的II类区域,可以编码异二聚体的两半。 有证据表明,加工机制的其他推定组分,LMP(低分子量多肽),也在MHC 13-15中编码。 LMPs和称为蛋白酶体的大的细胞内蛋白酶复合物的性质之间的相似性导致了LMPs参与加工抗原的建议16。 我们现在已经确定了一个与蛋白酶体组分具有序列同源性的人类基因。 值得注意的是,这个基因在两个假定的肽转运蛋白基因之间作图。
IT is now possible to paint a detailed picture of how cytoplasmic proteins are handled by the immune system 1-7. They are apparently degraded in the cytoplasm into peptides. These are then transported into the endoplasmic reticulum where they encounter class I major histocompatibility complex (MHC) molecules. Once loaded with peptide, the HLA molecules move through the Golgi apparatus to the cell membrane. Until recently, it had not been established how peptides without signal sequences cross the ER membrane. However, a number of papers have now described a pair of membrane transporter genes of the ABC (ATP-binding cassette) super-family which are attractive candidates for this function 8-12. Both transporter genes, which may encode two halves of a heterodimer, are situated in the class II region of the MHC. There is evidence that other putative components of the processing machinery, the LMPs (low molecular mass polypeptides), are also encoded in the MHC 13-15. Similarities between the properties of the LMPs and a large intracellular protease complex, called proteasome, have led to the suggestion that LMPs are involved in processing antigens 16. We have now identified a human gene with sequence homology to proteasome components. Remarkably, this gene maps between the two putative peptide transporter genes.