Effect of chaperone-client interaction strength on Hsp70-mediated protein folding

doi:10.1088/1674-1056/acea6f

中国物理B ›› 2023, Vol. 32 ›› Issue (11): 118701-118701.doi: 10.1088/1674-1056/acea6f

Effect of chaperone-client interaction strength on Hsp70-mediated protein folding

Lujun Zou(邹禄军)¹, Jiajun Lu(陆伽俊)¹, and Xiulian Xu(徐秀莲)^2,†

1 Department of Physics, National Laboratory of Solid State Microstructure, Nanjing University, Nanjing 210093, China;
2 School of Physics Science and Technology, Yangzhou University, Yangzhou 225002, China

收稿日期:2023-06-24 修回日期:2023-07-21 接受日期:2023-07-26 出版日期:2023-10-16 发布日期:2023-11-07
通讯作者: Xiulian Xu E-mail:xuxl@yzu.edu.cn
基金资助:
Project supported by the National Natural Science Foundation of China (Grant Nos. 11305139 and 11974173) and the HPC Center of Nanjing University.

Effect of chaperone-client interaction strength on Hsp70-mediated protein folding

Lujun Zou(邹禄军)¹, Jiajun Lu(陆伽俊)¹, and Xiulian Xu(徐秀莲)^2,†

1 Department of Physics, National Laboratory of Solid State Microstructure, Nanjing University, Nanjing 210093, China;
2 School of Physics Science and Technology, Yangzhou University, Yangzhou 225002, China

Received:2023-06-24 Revised:2023-07-21 Accepted:2023-07-26 Online:2023-10-16 Published:2023-11-07
Contact: Xiulian Xu E-mail:xuxl@yzu.edu.cn
Supported by:
Project supported by the National Natural Science Foundation of China (Grant Nos. 11305139 and 11974173) and the HPC Center of Nanjing University.

摘要/Abstract

摘要： Protein folding in crowding cellular environment often relies on the assistance of various chaperones. Hsp70 is one of the most ubiquitous chaperones in cells. Previous studies showed that the chaperone-client interactions at the open state tend to remodel the protein folding energy landscape and direct the protein folding as a foldase. In this work, we further investigate how the chaperone-client interaction strength modulates the foldase function of Hsp70 by using molecular simulations. The results showed that the time of substrate folding (including the whole folding step and substrate release step) has a non-monotonic dependence on the interaction strength. With the increasing of the chaperone-client interaction strength, the folding time decreases first, and then increases. More detailed analysis showed that when the chaperone-client interaction is too strong, even small number of chaperones-client contacts can maintain the substrate bound with the chaperone. The sampling of the transient chaperones-client complex with sparse inter-molecule contacts makes the client protein have chance to access the misfolded state even it is bound with chaperone. The current results suggest that the interaction strength is an important factor controlling the Hsp70 chaperoning function.

关键词: protein folding, molecular chaperone, molecular dynamics, Hsp70

Abstract: Protein folding in crowding cellular environment often relies on the assistance of various chaperones. Hsp70 is one of the most ubiquitous chaperones in cells. Previous studies showed that the chaperone-client interactions at the open state tend to remodel the protein folding energy landscape and direct the protein folding as a foldase. In this work, we further investigate how the chaperone-client interaction strength modulates the foldase function of Hsp70 by using molecular simulations. The results showed that the time of substrate folding (including the whole folding step and substrate release step) has a non-monotonic dependence on the interaction strength. With the increasing of the chaperone-client interaction strength, the folding time decreases first, and then increases. More detailed analysis showed that when the chaperone-client interaction is too strong, even small number of chaperones-client contacts can maintain the substrate bound with the chaperone. The sampling of the transient chaperones-client complex with sparse inter-molecule contacts makes the client protein have chance to access the misfolded state even it is bound with chaperone. The current results suggest that the interaction strength is an important factor controlling the Hsp70 chaperoning function.

Key words: protein folding, molecular chaperone, molecular dynamics, Hsp70

中图分类号: (Molecular dynamics simulation)

87.10.Tf

87.14.E- (Proteins) 87.15.Cc (Folding: thermodynamics, statistical mechanics, models, and pathways) 87.15.hm (Folding dynamics)

Lujun Zou(邹禄军), Jiajun Lu(陆伽俊), and Xiulian Xu(徐秀莲). Effect of chaperone-client interaction strength on Hsp70-mediated protein folding[J]. 中国物理B, 2023, 32(11): 118701-118701.

Lujun Zou(邹禄军), Jiajun Lu(陆伽俊), and Xiulian Xu(徐秀莲). Effect of chaperone-client interaction strength on Hsp70-mediated protein folding[J]. Chin. Phys. B, 2023, 32(11): 118701-118701.

参考文献

[1] Dobson C M 2003 Nature 426 884
[2] Leopold P E, Montal M and Onuchic J N 1992 Proc. Natl. Acad. Sci. 89 8721
[3] Onuchic J N, Luthey-Schulten Z and Wolynes P G 1997 Annu. Rev. Phys. Chem. 48 545
[4] Shea J E, Onuchic J N and Brooks III C L 1999 Proc. Natl. Acad. Sci. 96 12512
[5] Tzul F O, Vasilchuk D and Makhatadze G I 2017 Proc. Natl. Acad. Sci. 114 E1627
[6] Ferreiro D U, Hegler J A, Komives E A and Wolynes P G 2007 Proc. Natl. Acad. Sci. 104 19819
[7] Li W, Wolynes P G and Takada S 2011 Proc. Natl. Acad. Sci. 108 3504
[8] Li W, Wang W and Takada S 2014 Proc. Natl. Acad. Sci. 111 10550
[9] Li W, Wang J, Zhang J, Takada S and Wang W 2019 Phys. Rev. Lett. 122 238102
[10] Gianni S, Camilloni C, Giri R, et al. 2014 Proc. Natl. Acad. Sci. 111 14141
[11] Ellis R J 2001 Trends Biochem. Sci 26 597
[12] Dobson C M 2001 Phil. Trans. R. Soc. Lond. B 356 133
[13] Thirumalai D and Lorimer G H 2001 Annu. Rev. Biophys. Biomol. Struct. 30 245
[14] Bukau B and Horwich A L 1998 Cell 92 351
[15] Wang W, Vinocur B, Shoseyov O and Altman A 2004 Trends Plant Sci. 9 244
[16] Mayer M P 2013 Trends Biochem. Sci. 38 507
[17] Rosenzweig R, Nillegoda N B, Mayer M P and Bukau B 2019 Nat. Rev. Mol. Cell Biol. 20 665
[18] Clerico E M, Tilitsky J M, Meng W and Gierasch L M 2015 J. Mol. Biol. 427 1575
[19] Goloubinoff P and De Los Rios P 2007 Trends Biochem. Sci. 32 372
[20] Sharma S K, De Los Rios P, Christen P, Lustig A and Goloubinoff P 2010 Nat. Chem. Biol. 6 914
[21] Lu J, Zhang X, Wu Y, Sheng Y, Li W and Wang W 2021 Biophys. J. 120 1971
[22] Sekhar A, Rosenzweig R, Bouvignies G and Kay L E 2015 Proc. Natl. Acad. Sci. 112 10395
[23] Rüdiger S, Germeroth L, Schneider-Mergener J and Bukau B 1997 EMBO J 16 1501
[24] Sekhar A, Rosenzweig R, Bouvignies G and Kay L E 2016 Proc. Proc. Natl. Acad. Sci. 113 E2794
[25] Lindorff-Larsen K, Piana S, Dror R O and Shaw D E 2011 Science 334 517
[26] Tang Y, Yao Y and Wei G 2020 Chin. Phys. B 29 108710
[27] Zhang C and Zhou X 2020 Chin. Phys. B 29 108706
[28] Takada S, Kanada R, Tan C, Terakawa T, Li W and Kenzaki H 2015 Acc. Chem. Res. 48 3026
[29] Zhang W and Zhang J 2021 Chin. Phys. B 30 108703
[30] Zhu W, Li W and Wang W 2021 Chin. Phys. B 30 078701
[31] Nishikawa T, Nagadoi A, Yoshimura S, Aimoto S and Nishimura Y 1998 Structure 6 1057
[32] Zahn M, Berthold N, Kieslich B, Knappe D, Hoffmann R and Sträter N 2013 J. Mol. Biol. 425 2463
[33] Terakawa T and Takada S 2011 Biophys. J. 101 1450
[34] Li W, Terakawa T, Wang W and Takada S 2012 Proc. Natl. Acad. Sci. 109 17789
[35] Go N 1983 Annu. Rev. Biophys. Bioeng. 12 183
[36] Clementi C, Nymeyer H and Onuchic J N 2000 J. Mol. Biol. 298 937
[37] Li W, Yoshii H, Hori N, Kameda T and Takada S 2010 Methods 52 106
[38] Takada S 2012 Curr. Opin. Struct. Biol. 22 130
[39] Kim Y C and Hummer G 2008 J. Mol. Biol. 375 1416
[40] Jackson M B 2006 Molecular and Cellular Biophysics (Cambridge:Cambridge University Press) pp. 279-283
[41] Okazaki K I, Koga N, Takada S, Onuchic J N and Wolynes P G 2006 Proc. Natl. Acad. Sci. 103 11844
[42] Bertelsen E B, Chang L, Gestwicki J E and Zuiderweg E R 2009 Proc. Natl. Acad. Sci. 106 8471
[43] Zhuravleva A, Clerico E M and Gierasch L M 2012 Cell 151 1296
[44] Li W, Wang J, Zhang J and Wang W 2015 Curr. Opin. Struct. Biol. 30 25
[45] Lu J, Scheerer D, Haran G, Li W and Wang W 2022 J. Phys. Chem. B 126 8188
[46] Zhang Y, Chen M, Lu J, Li W, Wolynes P G and Wang W 2022 J. Phys. Chem. B 126 6792
[47] Zhang W, Cao Y, Li W and Wang W 2021 New J. Phys. 23 123010
[48] Kenzaki H, Koga N, Hori N, et al. 2011 J. Chem. Theory Comput. 7 1979
[49] DeLano W L 2009 The PyMOL Molecular Graphics System (DeLano Scientific:San Carlos, CA)
[50] Humphrey W, Dalke A and Schulten K 1996 J. Mol. Graphics 14 33
[51] Fink A L 1999 Physiol. Rev. 79 425
[52] Hartl F U, Bracher A and Hayer-Hartl M 2011 Nature 475 324

Effect of chaperone-client interaction strength on Hsp70-mediated protein folding

Effect of chaperone-client interaction strength on Hsp70-mediated protein folding

RichHTML

PDF (PC)

赞

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

Metrics

本文评价

推荐阅读 0

[1]	Baoshuang Shang(尚宝双). Anelasticity to plasticity transition in a model two-dimensional amorphous solid[J]. 中国物理B, 2024, 33(1): 16102-016102.
[2]	Wansong Zhu(朱万松), Zhenfa Zheng(郑镇法), Qijing Zheng(郑奇靖), and Jin Zhao(赵瑾). Ab initio nonadiabatic molecular dynamics study on spin-orbit coupling induced spin dynamics in ferromagnetic metals[J]. 中国物理B, 2024, 33(1): 16301-016301.
[3]	Xi He(何茜), Ziyi Xu(徐子翼), and Yushan Ni(倪玉山). Temperature effect on nanotwinned Ni under nanoindentation using molecular dynamic simulation[J]. 中国物理B, 2024, 33(1): 16201-016201.
[4]	Zhuoqun Zheng(郑卓群), Han Li(李晗), Zhu Su(宿柱), Nan Ding(丁楠), Xu Xu(徐旭),Haifei Zhan(占海飞), and Lifeng Wang(王立峰). Size effect on transverse free vibrations of ultrafine nanothreads[J]. 中国物理B, 2023, 32(9): 96202-096202.
[5]	Xin-Guan Tan(谭新官), Xue-Feng Liu(刘雪峰), Ming-Hui Pang(庞铭慧), Yu-Qing Wang(王雨晴), and Yun-Jie Zhao(赵蕴杰). Exploring unbinding mechanism of drugs from SERT via molecular dynamics simulation and its implication in antidepressants[J]. 中国物理B, 2023, 32(8): 88702-088702.
[6]	Lei Huang(黄磊), Kai Ren(任凯), Huanping Zhang(张焕萍), and Huasong Qin(覃华松). Enhanced mechanical and thermal properties of two-dimensional SiC and GeC with temperature and size dependence[J]. 中国物理B, 2023, 32(7): 76103-076103.
[7]	Xiang Ji(姬祥) and Junqian Zhang(张俊乾). Strain effects on Li⁺ diffusion in solid electrolyte interphases: A molecular dynamics study[J]. 中国物理B, 2023, 32(6): 66601-066601.
[8]	Minrong An(安敏荣), Yuefeng Lei(雷岳峰), Mengjia Su(宿梦嘉), Lanting Liu(刘兰亭), Qiong Deng(邓琼), Haiyang Song(宋海洋), Yu Shang(尚玉), and Chen Wang(王晨). Layer thickness dependent plastic deformation mechanism in Ti/TiCu dual-phase nano-laminates[J]. 中国物理B, 2023, 32(6): 66201-066201.
[9]	Yun-Chun Liu(刘云春), Yong-Chao Liang(梁永超), Qian Chen(陈茜), Li Zhang(张利), Jia-Jun Ma(马家君), Bei Wang(王蓓), Ting-Hong Gao(高廷红), and Quan Xie(谢泉). Dislocation mechanism of Ni₄₇Co₅₃ alloy during rapid solidification[J]. 中国物理B, 2023, 32(6): 66104-066104.
[10]	Ying Tang(唐莹), Junkun Liu(刘俊坤), Zihao Yu(于子皓), Ligang Sun(孙李刚), and Linli Zhu(朱林利). Molecular dynamics study on the dependence of thermal conductivity on size and strain in GaN nanofilms[J]. 中国物理B, 2023, 32(6): 66502-066502.
[11]	Zixuan Song(宋姿璇), Ziyue Zhou(周子岳), Yanwen Lin(林演文), Qiao Shi(石桥), Yongchao Hao(郝勇超),Yuequn Fu(付越群), Zhisen Zhang(张志森), and Jianyang Wu(吴建洋). Hydrogen diffusion in C₁' phase clathrate hydrate[J]. 中国物理B, 2023, 32(6): 66602-066602.
[12]	Min Zheng(郑敏), Jie Chen(陈杰), Zong-Xiao Zhu(朱宗孝), Ding-Feng Qu(曲定峰), Wei-Hua Chen(陈卫华), Zhuo Wu(吴卓), Lin-Jun Wang(王林军), and Xue-Zhong Ma(马学忠). Study of metal-ceramic WC/Cu nano-wear behavior and strengthening mechanism[J]. 中国物理B, 2023, 32(4): 46801-046801.
[13]	Tao-Wen Xiong(熊涛文), Xiao-Ping Chen(陈小平), Ye-Ping Lin(林也平), Xin-Fu He(贺新福), Wen Yang(杨文), Wang-Yu Hu(胡望宇), Fei Gao(高飞), and Hui-Qiu Deng(邓辉球). Molecular dynamics study of interactions between edge dislocation and irradiation-induced defects in Fe–10Ni–20Cr alloy[J]. 中国物理B, 2023, 32(2): 20206-020206.
[14]	Zilin Wang(王梓霖), Liang Yang(杨亮), Changsheng Liu(刘长生), and Shiwei Lin(林仕伟). Formation of nanobubbles generated by hydrate decomposition: A molecular dynamics study[J]. 中国物理B, 2023, 32(2): 23101-023101.
[15]	Jia-Hao Xiong(熊佳豪), Zi-Jun Qi(戚梓俊), Kang Liang(梁康), Xiang Sun(孙祥), Zhan-Peng Sun(孙展鹏), Qi-Jun Wang(汪启军), Li-Wei Chen(陈黎玮), Gai Wu(吴改), and Wei Shen(沈威). Molecular dynamics study of thermal conductivities of cubic diamond, lonsdaleite, and nanotwinned diamond via machine-learned potential[J]. 中国物理B, 2023, 32(12): 128101-128101.