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内质网氨肽酶 ERAP1 的分子尺机制的结构见解。

Structural insights into the molecular ruler mechanism of the endoplasmic reticulum aminopeptidase ERAP1.

机构信息

Department of Biological Sciences, University of Massachusetts Lowell, 1 University Avenue, Lowell, MA 01854, USA.

出版信息

Sci Rep. 2011;1:186. doi: 10.1038/srep00186. Epub 2011 Dec 13.

DOI:10.1038/srep00186
PMID:22355701
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3240994/
Abstract

Endoplasmic reticulum aminopeptidase 1 (ERAP1) is an essential component of the immune system, because it trims peptide precursors and generates the N--restricted epitopes. To examine ERAP1's unique properties of length- and sequence-dependent processing of antigen precursors, we report a 2.3 Å resolution complex structure of the ERAP1 regulatory domain. Our study reveals a binding conformation of ERAP1 to the carboxyl terminus of a peptide, and thus provides direct evidence for the molecular ruler mechanism.

摘要

内质网氨肽酶 1(ERAP1)是免疫系统的重要组成部分,因为它能修剪肽前体并产生 N-限制表位。为了研究 ERAP1 对抗原前体的长度和序列依赖性加工的独特特性,我们报告了 ERAP1 调节域的 2.3Å 分辨率复合物结构。我们的研究揭示了 ERAP1 与肽羧基末端的结合构象,从而为分子标尺机制提供了直接证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2528/3240994/e8e88ae85063/srep00186-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2528/3240994/f9666fd745a6/srep00186-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2528/3240994/90da96df915a/srep00186-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2528/3240994/9bc4b01da25b/srep00186-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2528/3240994/e8e88ae85063/srep00186-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2528/3240994/f9666fd745a6/srep00186-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2528/3240994/90da96df915a/srep00186-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2528/3240994/9bc4b01da25b/srep00186-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2528/3240994/e8e88ae85063/srep00186-f4.jpg

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Proc Natl Acad Sci U S A. 2011 May 10;108(19):7745-50. doi: 10.1073/pnas.1101262108. Epub 2011 Apr 20.
2
Structural basis for antigenic peptide precursor processing by the endoplasmic reticulum aminopeptidase ERAP1.内质网氨肽酶 ERAP1 对抗原肽前体加工的结构基础。
Nat Struct Mol Biol. 2011 May;18(5):604-13. doi: 10.1038/nsmb.2021. Epub 2011 Apr 10.
3
iMOSFLM: a new graphical interface for diffraction-image processing with MOSFLM.
构象动力学与结构域关闭和底物结合相关,解释了 ERAP1 变构调节机制。
Nat Commun. 2021 Sep 6;12(1):5302. doi: 10.1038/s41467-021-25564-w.
4
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Immunobiology. 2021 Jul;226(4):152112. doi: 10.1016/j.imbio.2021.152112. Epub 2021 Jul 4.
5
Enhanced recombinant expression and purification of human IRAP for biochemical and crystallography studies.用于生化和晶体学研究的人胰岛素受体相关蛋白(IRAP)的增强重组表达与纯化。
Biochem Biophys Rep. 2021 Jun 9;27:101042. doi: 10.1016/j.bbrep.2021.101042. eCollection 2021 Sep.
6
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