首页> 美国卫生研究院文献>The Journal of Experimental Medicine >The protease inhibitor N-acetyl-L-leucyl-L-leucyl-leucyl-L- norleucinal decreases the pool of major histocompatibility complex class I-binding peptides and inhibits peptide trimming in the endoplasmic reticulum

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The protease inhibitor N-acetyl-L-leucyl-L-leucyl-leucyl-L- norleucinal decreases the pool of major histocompatibility complex class I-binding peptides and inhibits peptide trimming in the endoplasmic reticulum

机译：蛋白酶抑制剂N-乙酰基-L-亮氨酰-L-亮氨酰-亮氨酰-L-正亮氨酸减少主要组织相容性复合物I类结合肽的聚集并抑制内质网中的肽修整

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N-acetyl-L-leucyl-L-leucyl-L-norleucinal, (LLnL), which inhibits proteasomes in addition to other proteases, was found to prolong the association of major histocompatibility complex class I molecules with the transporters associated with antigen processing (TAP), and to slow their transport out of the endoplasmic reticulum (ER). LLnL induced a reversible accumulation of ubiquitinated proteins and changed the spectrum of peptides bound by class I molecules. These effects can probably be attributed to proteasome inhibition. Unexpectedly, in the TAP-deficient cell line .174, the rate of intracellular transport of human histocompatibility leukocyte antigen (HLA) A2 was also reduced by LLnL, and the generation of most HLA-A2-associated signal sequence peptides was inhibited. The inhibition of HLA-A2 transport in .174 cells was found to be less sensitive to LLnL than in wild-type cells, and a similar difference was found for a second protease inhibitor, benzyloxycarbonyl-L-leucyl-L-leucyl-L-phenylalanilal. These data suggest that under some conditions such inhibitors can block trimming of peptides by an ER peptidase in addition to inhibiting cytosolic peptide generation.

机译：发现N-乙酰基-L-亮氨酰-L-亮氨酰-L-净核糖核酸（LLnL）除其他蛋白酶外还抑制蛋白酶体，从而延长了主要组织相容性复合物I类分子与与抗原加工相关的转运蛋白的结合（ TAP），并减缓其从内质网（ER）的运输。 LLnL诱导了遍在蛋白的可逆积累，并改变了由I类分子结合的肽的光谱。这些作用可能归因于蛋白酶体的抑制。出乎意料的是，在TAP缺陷细胞系.174中，LLnL也降低了人类组织相容性白细胞抗原（HLA）A2的细胞内转运速率，并且抑制了大多数HLA-A2相关信号序列肽的产生。发现在.174细胞中对HLA-A2转运的抑制对LLnL的敏感性不如在野生型细胞中，对第二种蛋白酶抑制剂，苄氧羰基-L-亮氨酰-L-亮氨酰-L-苯丙氨醛这些数据表明，在某些条件下，此类抑制剂除了抑制胞质肽的生成外，还可以通过ER肽酶阻断肽的修饰。

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期刊名称 The Journal of Experimental Medicine
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年(卷),期 1996(183),4
年度 1996
页码 1569–1578
总页数 10
原文格式 PDF
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中图分类免疫学;医学史;
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1. The protease inhibitor, N-acetyl-L-leucyl-L-leucyl-leucyl-L-norleucinal, decreases the pool of major histocompatibility complex class I-binding peptides and inhibits peptide trimming in the endoplasmic reticulum. [J] . E A Hughes, B Ortmann, M Surman, The Journal of Experomental Medicine . 1996,第4期

机译：蛋白酶抑制剂，N-乙酰基-L-亮氨酰-L-亮氨酰-亮氨酰-L-净核糖核酸，可减少主要组织相容性复合物I类结合肽的汇集，并抑制内质网中的肽修整。
2. The protease inhibitor, N-acetyl-L-leucyl-L-leucyl-leucyl-L-norleucinal, decreases the pool of major histocompatibility complex class I-binding peptides and inhibits peptide trimming in the endoplasmic reticulum. [J] . E A Hughes, B Ortmann, M Surman, The Journal of Experomental Medicine . 1996,第4期

机译：蛋白酶抑制剂，N-乙酰基-L-亮氨酰-L-亮氨酰-亮氨酰-L-净核糖核酸，可减少主要组织相容性复合物I类结合肽的汇集，并抑制内质网中的肽修整。
3. Redox-regulated Export of the Major Histocompatibility Complex Class I-Peptide Complexes from the Endoplasmic Reticulum [J] . Sungwook Lee, Boyoun Park, Kwonyoon Kang, Molecular biology of the cell . 2009,第14期

机译：氧化还原调节的主要组织相容性复合物I类肽复合物从内质网的出口。
4. Invariant chain regulates the major histocompatibility complex class II peptide repertoire of cell-based cancer vaccines. [C] . Olesya Y. Chornoguz, Lydia Grmai, Alexei Gapeev, American Society for Mass Spectrometry Conference on Mass Spectrometry and Allied Topics . 2010

机译：不变链调节细胞基癌症疫苗的主要组织相容性复合体II类肽曲目。
5. Defining the mechanism of MHC class II peptide editing by HLA-DM: I. HLA-DM recognizes the flexible conformation of major histocompatibility complex class II. II. Mapping the interaction surface of DR1 with DM by superantigen blocking. III. Determinati [D] . Chou, Chih-Ling. 2003

机译：定义HLA-DM编辑MHC II类肽的机制：I. HLA-DM识别II类主要组织相容性复合物的柔性构象。二。通过超抗原阻断作用绘制DR1与DM的相互作用表面。三，确定性
6. Evidence that transporters associated with antigen processing translocate a major histocompatibility complex class I-binding peptide into the endoplasmic reticulum in an ATP-dependent manner. [O] . M J Androlewicz, K S Anderson, P Cresswell 1993

机译：与抗原加工相关的转运蛋白的证据表明一种主要的组织相容性复合物I类结合肽以ATP依赖性方式转移到内质网中。
7. The protease inhibitor, N-acetyl-L-leucyl-L-leucyl-leucyl-L- norleucinal, decreases the pool of major histocompatibility complex class I-binding peptides and inhibits peptide trimming in the endoplasmic reticulum [O] . 1996

机译：蛋白酶抑制剂N-乙酰基-L-亮氨酰-L-亮氨酰-亮氨酰-L-正芥子碱可减少主要组织相容性复合物I类结合肽的聚集并抑制内质网中的肽修整
8. Quinolinol and Peptide Inhibitors of Zinc Protease in Botulinum Neurotoxin A: Effects of Zinc Ion and Peptides on Inhibition [R] . Lai, H., Feng, M., Roxas-Duncan, V., 2009

机译：肉毒杆菌神经毒素a中锌羟基喹啉和锌蛋白酶抑制剂：锌离子和肽对抑制作用的影响

The protease inhibitor N-acetyl-L-leucyl-L-leucyl-leucyl-L- norleucinal decreases the pool of major histocompatibility complex class I-binding peptides and inhibits peptide trimming in the endoplasmic reticulum

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