热休克蛋白90（Hsp90）-细胞周期蛋白依赖性激酶37（Cdc37）-细胞周期蛋白依赖性激酶4（Cdk4）复合物的结构
Structure of an Hsp90-Cdc37-Cdk4 complex.
作者信息
Vaughan Cara K, Gohlke Ulrich, Sobott Frank, Good Valerie M, Ali Maruf M U, Prodromou Chrisostomos, Robinson Carol V, Saibil Helen R, Pearl Laurence H
机构信息
Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, London SW3 6JB, UK.
出版信息
Mol Cell. 2006 Sep 1;23(5):697-707. doi: 10.1016/j.molcel.2006.07.016.
Abstract
Activation of many protein kinases depends on their interaction with the Hsp90 molecular chaperone system. Recruitment of protein kinase clients to the Hsp90 chaperone system is mediated by the cochaperone adaptor protein Cdc37, which acts as a scaffold, simultaneously binding protein kinases and Hsp90. We have now expressed and purified an Hsp90-Cdc37-Cdk4 complex, defined its stoichiometry, and determined its 3D structure by single-particle electron microscopy. Comparison with the crystal structure of Hsp90 allows us to identify the locations of Cdc37 and Cdk4 in the complex and suggests a mechanism by which conformational changes in the kinase are coupled to the Hsp90 ATPase cycle.
摘要
许多蛋白激酶的激活依赖于它们与热休克蛋白90（Hsp90）分子伴侣系统的相互作用。蛋白激酶底物被招募到Hsp90伴侣系统是由共伴侣衔接蛋白Cdc37介导的，Cdc37作为一个支架，同时结合蛋白激酶和Hsp90。我们现已表达并纯化了Hsp90-Cdc37-Cdk4复合物，确定了其化学计量，并通过单颗粒电子显微镜确定了其三维结构。与Hsp90晶体结构的比较使我们能够确定复合物中Cdc37和Cdk4的位置，并提出了一种激酶构象变化与Hsp90 ATP酶循环偶联的机制。
相似文献
1
Structure of an Hsp90-Cdc37-Cdk4 complex.热休克蛋白90（Hsp90）-细胞周期蛋白依赖性激酶37（Cdc37）-细胞周期蛋白依赖性激酶4（Cdk4）复合物的结构
Mol Cell. 2006 Sep 1;23(5):697-707. doi: 10.1016/j.molcel.2006.07.016.
2
Atomic structure of Hsp90-Cdc37-Cdk4 reveals that Hsp90 traps and stabilizes an unfolded kinase.Hsp90-Cdc37-Cdk4 的原子结构揭示了 Hsp90 捕获并稳定未折叠激酶。
Science. 2016 Jun 24;352(6293):1542-7. doi: 10.1126/science.aaf5023.
3
Atomistic simulations and network-based modeling of the Hsp90-Cdc37 chaperone binding with Cdk4 client protein: A mechanism of chaperoning kinase clients by exploiting weak spots of intrinsically dynamic kinase domains.热休克蛋白90（Hsp90）-细胞周期蛋白依赖性激酶37（Cdc37）伴侣蛋白与细胞周期蛋白依赖性激酶4（Cdk4）客户蛋白结合的原子模拟和基于网络的建模：通过利用内在动态激酶结构域的弱点来陪伴激酶客户的机制
PLoS One. 2017 Dec 21;12(12):e0190267. doi: 10.1371/journal.pone.0190267. eCollection 2017.
4
Functional Role and Hierarchy of the Intermolecular Interactions in Binding of Protein Kinase Clients to the Hsp90-Cdc37 Chaperone: Structure-Based Network Modeling of Allosteric Regulation.蛋白质激酶客户与 Hsp90-Cdc37 伴侣蛋白结合的分子间相互作用的功能作用和层次：变构调节的基于结构的网络建模。
J Chem Inf Model. 2018 Feb 26;58(2):405-421. doi: 10.1021/acs.jcim.7b00638. Epub 2018 Feb 15.
5
Hsp90·Cdc37 Complexes with Protein Kinases Form Cooperatively with Multiple Distinct Interaction Sites.热休克蛋白90·细胞分裂周期蛋白37复合物与蛋白激酶通过多个不同的相互作用位点协同形成。
J Biol Chem. 2015 Dec 25;290(52):30843-54. doi: 10.1074/jbc.M115.693150. Epub 2015 Oct 28.
6
Characterization of celastrol to inhibit hsp90 and cdc37 interaction.鉴定雷公藤红素抑制 HSP90 和 Cdc37 相互作用。
J Biol Chem. 2009 Dec 18;284(51):35381-9. doi: 10.1074/jbc.M109.051532.
7
Restricting direct interaction of CDC37 with HSP90 does not compromise chaperoning of client proteins.限制CDC37与HSP90的直接相互作用不会损害客户蛋白的伴侣功能。
Oncogene. 2015 Jan 2;34(1):15-26. doi: 10.1038/onc.2013.519. Epub 2013 Dec 2.
8
Allosteric CDC37 Inhibitor Disrupts Chaperone Complex to Block CDK4/6 Maturation.变构CDC37抑制剂破坏伴侣蛋白复合物以阻断CDK4/6成熟。
Angew Chem Int Ed Engl. 2025 Jan 10;64(2):e202413618. doi: 10.1002/anie.202413618. Epub 2024 Dec 2.
9
Differential Regulation of G1 CDK Complexes by the Hsp90-Cdc37 Chaperone System.Hsp90-Cdc37 伴侣系统对 G1 CDK 复合物的差异调控。
Cell Rep. 2017 Oct 31;21(5):1386-1398. doi: 10.1016/j.celrep.2017.10.042.
10
Molecular Mechanism of Protein Kinase Recognition and Sorting by the Hsp90 Kinome-Specific Cochaperone Cdc37.热休克蛋白90激酶组特异性伴侣蛋白Cdc37对蛋白激酶的识别与分选的分子机制
Mol Cell. 2016 Apr 21;62(2):260-271. doi: 10.1016/j.molcel.2016.04.005.
引用本文的文献
1
Benzbromarone interferes with the interaction between Hsp90 and Aha1 by interacting with both of them.苯溴马隆通过与热休克蛋白90（Hsp90）和Aha1两者相互作用，干扰它们之间的相互作用。
Commun Biol. 2025 May 16;8(1):761. doi: 10.1038/s42003-025-08189-3.
2
Structural dynamics of RAF1-HSP90-CDC37 and HSP90 complexes reveal asymmetric client interactions and key structural elements.RAF1-HSP90-CDC37和HSP90复合物的结构动力学揭示了不对称的客户相互作用和关键结构元件。
Commun Biol. 2024 Mar 2;7(1):260. doi: 10.1038/s42003-024-05959-3.
3
Establishing Order Through Disorder by the Hsp90 Molecular Chaperone.通过热休克蛋白 90 分子伴侣建立无序中的有序。
J Mol Biol. 2024 Jul 15;436(14):168460. doi: 10.1016/j.jmb.2024.168460. Epub 2024 Jan 30.
4
TTT (Tel2-Tti1-Tti2) Complex, the Co-Chaperone of PIKKs and a Potential Target for Cancer Chemotherapy.TTT（Tel2-Tti1-Tti2）复合物，PIKKs 的共伴侣，癌症化疗的潜在靶点。
Int J Mol Sci. 2023 May 5;24(9):8268. doi: 10.3390/ijms24098268.
5
Organismal Roles of Hsp90.Hsp90 的机体角色。
Biomolecules. 2023 Jan 29;13(2):251. doi: 10.3390/biom13020251.
6
Impact of Co-chaperones and Posttranslational Modifications Toward Hsp90 Drug Sensitivity.共伴侣蛋白和翻译后修饰对Hsp90药物敏感性的影响
Subcell Biochem. 2023;101:319-350. doi: 10.1007/978-3-031-14740-1_11.
7
The Chaperone System in Salivary Glands: Hsp90 Prospects for Differential Diagnosis and Treatment of Malignant Tumors.唾液腺中的伴侣蛋白系统：Hsp90 作为恶性肿瘤鉴别诊断和治疗的新靶点。
Int J Mol Sci. 2022 Aug 18;23(16):9317. doi: 10.3390/ijms23169317.
8
Aha1 Is an Autonomous Chaperone for SULT1A1.Aha1 是 SULT1A1 的自主伴侣蛋白。
Chem Res Toxicol. 2022 Aug 15;35(8):1418-1424. doi: 10.1021/acs.chemrestox.2c00167. Epub 2022 Aug 4.
9
TRAP1 Chaperones the Metabolic Switch in Cancer.TRAP1在癌症中陪伴代谢转换。
Biomolecules. 2022 Jun 4;12(6):786. doi: 10.3390/biom12060786.
10
Advances towards Understanding the Mechanism of Action of the Hsp90 Complex.理解 HSP90 复合物作用机制的研究进展。
Biomolecules. 2022 Apr 19;12(5):600. doi: 10.3390/biom12050600.
本文引用的文献
1
Crystal structure of an Hsp90-nucleotide-p23/Sba1 closed chaperone complex.热休克蛋白90-核苷酸-p23/Sba1封闭伴侣复合物的晶体结构
Nature. 2006 Apr 20;440(7087):1013-7. doi: 10.1038/nature04716.
2
A client-binding site of Cdc37.细胞周期蛋白依赖性激酶37（Cdc37）的一个客户蛋白结合位点。
FEBS J. 2005 Sep;272(18):4684-90. doi: 10.1111/j.1742-4658.2005.04884.x.
3
Domain-mediated dimerization of the Hsp90 cochaperones Harc and Cdc37.热休克蛋白90辅助伴侣蛋白Harc和Cdc37的结构域介导的二聚化
Biochemistry. 2005 May 3;44(17):6662-9. doi: 10.1021/bi047406z.
4
Structures of the N-terminal and middle domains of E. coli Hsp90 and conformation changes upon ADP binding.大肠杆菌Hsp90的N端和中间结构域的结构以及ADP结合后的构象变化。
Structure. 2005 Apr;13(4):579-90. doi: 10.1016/j.str.2004.12.018.
5
Hsp90 and Cdc37 -- a chaperone cancer conspiracy.热休克蛋白90（Hsp90）与Cdc37——伴侣蛋白与癌症的共谋。
Curr Opin Genet Dev. 2005 Feb;15(1):55-61. doi: 10.1016/j.gde.2004.12.011.
6
Surface charge and hydrophobicity determine ErbB2 binding to the Hsp90 chaperone complex.表面电荷和疏水性决定了ErbB2与热休克蛋白90（Hsp90）伴侣复合物的结合。
Nat Struct Mol Biol. 2005 Feb;12(2):120-6. doi: 10.1038/nsmb885. Epub 2005 Jan 9.
7
Co-chaperone regulation of conformational switching in the Hsp90 ATPase cycle.共伴侣蛋白对Hsp90 ATP酶循环中构象转换的调控
J Biol Chem. 2004 Dec 10;279(50):51989-98. doi: 10.1074/jbc.M410562200. Epub 2004 Oct 2.
8
Investigation of intact protein complexes by mass spectrometry.通过质谱法对完整蛋白质复合物进行研究。
Mass Spectrom Rev. 2004 Sep-Oct;23(5):368-89. doi: 10.1002/mas.10081.
9
Definition of protein kinase sequence motifs that trigger high affinity binding of Hsp90 and Cdc37.触发Hsp90和Cdc37高亲和力结合的蛋白激酶序列基序的定义。
J Biol Chem. 2004 Sep 17;279(38):39975-81. doi: 10.1074/jbc.M406882200. Epub 2004 Jul 17.
10
Biochemical and structural studies of the interaction of Cdc37 with Hsp90.Cdc37与Hsp90相互作用的生化及结构研究。
J Mol Biol. 2004 Jul 16;340(4):891-907. doi: 10.1016/j.jmb.2004.05.007.
Zotero 插件