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CypA 与 AIF 相互作用的结构和生化研究进展

Structural and biochemical insights of CypA and AIF interaction.

机构信息

Istituto di Biostrutture e Bioimmagini, C.N.R. and CIRPEB, Via Mezzocannone 16, 80134, Napoli, Italy.

Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Università degli Studi della Campania Luigi Vanvitelli, via Vivaldi 46, 81100, Caserta, Italy.

出版信息

Sci Rep. 2017 Apr 25;7(1):1138. doi: 10.1038/s41598-017-01337-8.

DOI:10.1038/s41598-017-01337-8
PMID:28442737
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5430804/
Abstract

The Cyclophilin A (CypA)/Apoptosis Inducing Factor (AIF) complex is implicated in the DNA degradation in response to various cellular stress conditions, such as oxidative stress, cerebral hypoxia-ischemia and traumatic brain injury. The pro-apoptotic form of AIF (AIF(Δ1-121)) mainly interacts with CypA through the amino acid region 370-394. The AIF(370-394) synthetic peptide inhibits complex formation in vitro by binding to CypA and exerts neuroprotection in a model of glutamate-mediated oxidative stress. Here, the binding site of AIF(Δ1-121) and AIF(370-394) on CypA has been mapped by NMR spectroscopy and biochemical studies, and a molecular model of the complex has been proposed. We show that AIF(370-394) interacts with CypA on the same surface recognized by AIF(Δ1-121) protein and that the region is very close to the CypA catalytic pocket. Such region partially overlaps with the binding site of cyclosporin A (CsA), the strongest catalytic inhibitor of CypA. Our data point toward distinct CypA structural determinants governing the inhibitor selectivity and the differential biological effects of AIF and CsA, and provide new structural insights for designing CypA/AIF selective inhibitors with therapeutic relevance in neurodegenerative diseases.

摘要

亲环素 A（CypA）/凋亡诱导因子（AIF）复合物与各种细胞应激条件下的 DNA 降解有关，如氧化应激、脑缺氧缺血和创伤性脑损伤。促凋亡形式的 AIF（AIF（Δ1-121））主要通过氨基酸区域 370-394 与 CypA 相互作用。AIF（370-394）合成肽通过与 CypA 结合在体外抑制复合物形成，并在谷氨酸介导的氧化应激模型中发挥神经保护作用。在这里，通过 NMR 光谱和生化研究映射了 AIF（Δ1-121）和 AIF（370-394）在 CypA 上的结合位点，并提出了复合物的分子模型。我们表明，AIF（370-394）与 CypA 相互作用的表面与 AIF（Δ1-121）蛋白识别的表面相同，并且该区域非常接近 CypA 催化口袋。该区域与环孢菌素 A（CsA）的结合位点部分重叠，环孢菌素 A 是 CypA 的最强催化抑制剂。我们的数据表明，CypA 的结构决定因素决定了抑制剂的选择性和 AIF 和 CsA 的不同生物学效应，并为设计具有神经退行性疾病治疗相关性的 CypA/AIF 选择性抑制剂提供了新的结构见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad49/5430804/c9e85909f522/41598_2017_1337_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad49/5430804/944e712e4c2d/41598_2017_1337_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad49/5430804/553cea2c6c39/41598_2017_1337_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad49/5430804/ffa15013a905/41598_2017_1337_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad49/5430804/a4a1b91cf878/41598_2017_1337_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad49/5430804/69748a2606a9/41598_2017_1337_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad49/5430804/c9e85909f522/41598_2017_1337_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad49/5430804/944e712e4c2d/41598_2017_1337_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad49/5430804/553cea2c6c39/41598_2017_1337_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad49/5430804/ffa15013a905/41598_2017_1337_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad49/5430804/a4a1b91cf878/41598_2017_1337_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad49/5430804/69748a2606a9/41598_2017_1337_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad49/5430804/c9e85909f522/41598_2017_1337_Fig6_HTML.jpg

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本文引用的文献

1
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J Pept Sci. 2017 Apr;23(4):272-281. doi: 10.1002/psc.2977. Epub 2017 Jan 31.
2
FRET-Protease-Coupled Peptidyl-Prolyl cis-trans Isomerase Assay: New Internally Quenched Fluorogenic Substrates for High-Throughput Screening.荧光共振能量转移-蛋白酶偶联肽基脯氨酰顺反异构酶测定：用于高通量筛选的新型内部淬灭荧光底物
J Biomol Screen. 2016 Aug;21(7):701-12. doi: 10.1177/1087057116650402. Epub 2016 May 16.
3
Dynamical network of residue-residue contacts reveals coupled allosteric effects in recognition, catalysis, and mutation.
Parthanatos: Mechanisms, modulation, and therapeutic prospects in neurodegenerative disease and stroke.
细胞坏死性凋亡：神经退行性疾病和中风中的机制、调节及治疗前景。
Biochem Pharmacol. 2024 Oct;228:116174. doi: 10.1016/j.bcp.2024.116174. Epub 2024 Mar 27.
4
Targeting Protein-Protein Interfaces with Peptides: The Contribution of Chemical Combinatorial Peptide Library Approaches.靶向蛋白质-蛋白质界面的肽：化学组合肽文库方法的贡献。
Int J Mol Sci. 2023 Apr 25;24(9):7842. doi: 10.3390/ijms24097842.
5
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Sci Rep. 2022 Aug 29;12(1):14675. doi: 10.1038/s41598-022-19066-y.
6
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ChemMedChem. 2022 Jun 3;17(11):e202200050. doi: 10.1002/cmdc.202200050. Epub 2022 Apr 26.
7
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Proc Natl Acad Sci U S A. 2016 Apr 26;113(17):4735-40. doi: 10.1073/pnas.1523573113. Epub 2016 Apr 11.
4
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J Mol Biol. 2016 Feb 22;428(4):720-725. doi: 10.1016/j.jmb.2015.09.014. Epub 2015 Sep 26.
5
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6
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Nat Protoc. 2015 May;10(5):733-55. doi: 10.1038/nprot.2015.043. Epub 2015 Apr 9.
7
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J Pharmacol Exp Ther. 2014 Aug;350(2):273-89. doi: 10.1124/jpet.114.213777. Epub 2014 May 21.
8
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Cell Death Dis. 2014 Jan 16;5(1):e993. doi: 10.1038/cddis.2013.518.
9
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10
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Prog Nucl Magn Reson Spectrosc. 2013 Aug;73:1-16. doi: 10.1016/j.pnmrs.2013.02.001. Epub 2013 Mar 21.