凋亡半胱氨酸蛋白酶变构“关闭开关”的进化。
Evolution of an allosteric "off switch" in apoptotic caspases.
机构信息
From the Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267 and
Divisions of Immunobiology and Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati Ohio 45229.
出版信息
J Biol Chem. 2018 Apr 13;293(15):5462-5463. doi: 10.1074/jbc.H118.002379.
Abstract
Caspase-3 is well known as the "executioner" whose activation commits the cell to an apoptotic fate, but low levels of caspase-3 activity also play key roles in development. A new study explains how cells can balance these functions, using biophysical, structural, and computational approaches to demonstrate the mechanism by which phosphorylation of conserved sites on a distal surface loop reduces or abolishes catalytic activity. These results provide new insights into allosteric regulation mechanisms and offer new opportunities for development of caspase-3 modulators.
摘要
Caspase-3 是众所周知的“执行者”，其激活将细胞推向凋亡命运，但低水平的 caspase-3 活性在发育中也起着关键作用。一项新的研究解释了细胞如何平衡这些功能，它使用生物物理、结构和计算方法来证明在远端表面环的保守位点磷酸化如何降低或消除催化活性的机制。这些结果为别构调节机制提供了新的见解，并为 caspase-3 调节剂的开发提供了新的机会。
相似文献
1
Evolution of an allosteric "off switch" in apoptotic caspases.凋亡半胱氨酸蛋白酶变构“关闭开关”的进化。
J Biol Chem. 2018 Apr 13;293(15):5462-5463. doi: 10.1074/jbc.H118.002379.
2
Modifications to a common phosphorylation network provide individualized control in caspases.对常见磷酸化网络的修饰为半胱天冬酶提供了个性化控制。
J Biol Chem. 2018 Apr 13;293(15):5447-5461. doi: 10.1074/jbc.RA117.000728. Epub 2018 Feb 5.
3
Allosteric modulation of caspase 3 through mutagenesis.通过突变对胱冬肽酶 3 的变构调节。
Biosci Rep. 2012 Aug;32(4):401-11. doi: 10.1042/BSR20120037.
4
Identification of FDA-approved drugs as novel allosteric inhibitors of human executioner caspases.鉴定 FDA 批准的药物作为新型人效应子半胱氨酸蛋白酶的别构抑制剂。
Proteins. 2018 Nov;86(11):1202-1210. doi: 10.1002/prot.25601. Epub 2018 Oct 5.
5
Tunable allosteric library of caspase-3 identifies coupling between conserved water molecules and conformational selection.半胱天冬酶-3的可调变构文库确定了保守水分子与构象选择之间的耦合。
Proc Natl Acad Sci U S A. 2016 Oct 11;113(41):E6080-E6088. doi: 10.1073/pnas.1603549113. Epub 2016 Sep 28.
6
Phosphorylation by protein kinase A disassembles the caspase-9 core.蛋白激酶 A 的磷酸化使 caspase-9 核心解体。
Cell Death Differ. 2018 Jun;25(6):1025-1039. doi: 10.1038/s41418-017-0052-9. Epub 2018 Jan 19.
7
Caspase Allostery and Conformational Selection.半胱天冬氨酸蛋白酶变构和构象选择。
Chem Rev. 2016 Jun 8;116(11):6666-706. doi: 10.1021/acs.chemrev.5b00540. Epub 2016 Jan 11.
8
Conformational similarity in the activation of caspase-3 and -7 revealed by the unliganded and inhibited structures of caspase-7.无配体和抑制状态下 caspase-7 结构揭示的 caspase-3 和 -7 激活的构象相似性。
Apoptosis. 2009 Oct;14(10):1135-44. doi: 10.1007/s10495-009-0388-9.
9
A single-cell analytical approach to quantify activated caspase-3/7 during osteoblast proliferation, differentiation, and apoptosis.一种单细胞分析方法，用于定量测定成骨细胞增殖、分化和凋亡过程中激活的 Caspase-3/7。
Anal Bioanal Chem. 2021 Aug;413(20):5085-5093. doi: 10.1007/s00216-021-03471-9. Epub 2021 Jun 25.
10
Dissecting an allosteric switch in caspase-7 using chemical and mutational probes.使用化学和突变探针剖析半胱天冬酶-7中的变构开关。
J Biol Chem. 2009 Sep 18;284(38):26063-9. doi: 10.1074/jbc.M109.001826. Epub 2009 Jul 6.
引用本文的文献
1
Mechanism of apoptosis in oral squamous cell carcinoma promoted by cardamonin through PI3K/AKT signaling pathway.小豆蔻明通过 PI3K/AKT 信号通路促进口腔鳞状细胞癌细胞凋亡的机制。
Sci Rep. 2024 Sep 5;14(1):20802. doi: 10.1038/s41598-024-71817-1.
2
The potential effect and mechanism of Saikosaponin A against gastric cancer.柴胡皂苷 A 对胃癌的潜在作用及机制。
BMC Complement Med Ther. 2023 Aug 22;23(1):295. doi: 10.1186/s12906-023-04108-3.
3
Synthesis of Zinc Oxide (ZnO)-Titanium Dioxide (TiO)-Chitosan-Farnesol Nanocomposites and Assessment of Their Anticancer Potential in Human Leukemic MOLT-4 Cell Line.氧化锌（ZnO）-二氧化钛（TiO）-壳聚糖-法尼醇纳米复合材料的合成及其对人白血病MOLT-4细胞系抗癌潜力的评估
Bioinorg Chem Appl. 2022 Sep 28;2022:5949086. doi: 10.1155/2022/5949086. eCollection 2022.
4
Non-Apoptotic Caspase Activity Preferentially Targets a Novel Consensus Sequence Associated With Cytoskeletal Proteins in the Developing Auditory Brainstem.非凋亡性半胱天冬酶活性优先靶向发育中的听觉脑干中与细胞骨架蛋白相关的新共有序列。
Front Cell Dev Biol. 2022 Mar 7;10:844844. doi: 10.3389/fcell.2022.844844. eCollection 2022.
5
D-carvone induced ROS mediated apoptotic cell death in human leukemic cell lines (Molt-4).D-香芹酮通过活性氧介导人白血病细胞系（Molt-4）发生凋亡性细胞死亡。
Bioinformation. 2021 Jan 31;17(1):171-180. doi: 10.6026/97320630017171. eCollection 2021.
6
Survivin and caspases serum protein levels and survivin variants mRNA expression in sepsis.脓毒症患者血清中存活素和半胱天冬酶蛋白水平及存活素变异体 mRNA 表达
Sci Rep. 2021 Jan 13;11(1):1049. doi: 10.1038/s41598-020-78208-2.
7
Cell Communications among Microorganisms, Plants, and Animals: Origin, Evolution, and Interplays.微生物、植物和动物之间的细胞通讯：起源、进化和相互作用。
Int J Mol Sci. 2020 Oct 28;21(21):8052. doi: 10.3390/ijms21218052.
8
A 200 nanoseconds all-atom simulation of the pH-dependent EF loop transition in bovine β-lactoglobulin. The role of the orientation of the E89 side chain.牛β-乳球蛋白中 pH 依赖的 EF 环构象转变的 200 纳秒全原子模拟。E89 侧链取向的作用。
J Biomol Struct Dyn. 2022 Jan;40(1):549-564. doi: 10.1080/07391102.2020.1817785. Epub 2020 Sep 10.
9
Promising Antineoplastic Actions of Melatonin.褪黑素具有潜在的抗肿瘤作用。
Front Pharmacol. 2018 Oct 16;9:1086. doi: 10.3389/fphar.2018.01086. eCollection 2018.
本文引用的文献
1
Modifications to a common phosphorylation network provide individualized control in caspases.对常见磷酸化网络的修饰为半胱天冬酶提供了个性化控制。
J Biol Chem. 2018 Apr 13;293(15):5447-5461. doi: 10.1074/jbc.RA117.000728. Epub 2018 Feb 5.
2
Caspase substrates and inhibitors.半胱天冬酶底物和抑制剂。
Cold Spring Harb Perspect Biol. 2013 Aug 1;5(8):a008680. doi: 10.1101/cshperspect.a008680.
3
Cellular mechanisms controlling caspase activation and function.细胞机制控制半胱氨酸天冬氨酸蛋白酶的激活和功能。
Cold Spring Harb Perspect Biol. 2013 Jun 1;5(6):a008672. doi: 10.1101/cshperspect.a008672.
4
Caspase substrates and cellular remodeling.半胱天冬酶底物与细胞重塑。
Annu Rev Biochem. 2011;80:1055-87. doi: 10.1146/annurev-biochem-061809-121639.
5
Neuronal caspase-3 signaling: not only cell death.神经元 Caspase-3 信号：不只是细胞死亡。
Cell Death Differ. 2010 Jul;17(7):1104-14. doi: 10.1038/cdd.2009.180. Epub 2009 Dec 4.
6
Human caspases: activation, specificity, and regulation.人类半胱天冬酶：激活、特异性及调控
J Biol Chem. 2009 Aug 14;284(33):21777-21781. doi: 10.1074/jbc.R800084200. Epub 2009 May 26.
7
p38-MAPK signals survival by phosphorylation of caspase-8 and caspase-3 in human neutrophils.p38丝裂原活化蛋白激酶通过磷酸化人中性粒细胞中的半胱天冬酶-8和半胱天冬酶-3来传递生存信号。
J Exp Med. 2004 Feb 16;199(4):449-58. doi: 10.1084/jem.20031771.
8
S-Nitrosylation of mitochondrial caspases.线粒体半胱天冬酶的S-亚硝基化
J Cell Biol. 2001 Sep 17;154(6):1111-6. doi: 10.1083/jcb.200104008. Epub 2001 Sep 10.
Zotero 插件