Steered molecular dynamics simulation of the binding of the bovine auxilin J domain to the Hsc70 nucleotide-binding domain
Steered molecular dynamics simulation of the binding of the bovine auxilin J domain to the Hsc70 nucleotide-binding domain
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牛辅助素 J 结构域与 Hsc70 核苷酸结合结构域结合的引导分子动力学模拟
DOI：
10.1007/s00894-017-3453-2
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发表时间：
2017-10
影响因子：
2.2
通讯作者：
Song Youtao
中科院分区：
文献类型：
--
作者：
Xue Youlin;Zhou Lei;Sun Yuna;Li Hui;Jones Gary W.;Song Youtao
The Hsp70 and Hsp40 chaperone machine plays critical roles in protein folding, membrane translocation, and protein degradation by binding and releasing protein substrates in a process that utilizes ATP. The activities of the Hsp70 family of chaperones are recruited and stimulated by the J domains of Hsp40 chaperones. However, structural information on the Hsp40–Hsp70 complex is lacking, and the molecular details of this interaction are yet to be elucidated. Here we used steered molecular dynamics (SMD) simulations to investigate the molecular interactions that occur during the dissociation of the auxilin J domain from the Hsc70 nucleotide-binding domain (NBD). The changes in energy observed during the SMD simulation suggest that electrostatic interactions are the dominant type of interaction. Additionally, we found that Hsp70 mainly interacts with auxilin through the surface residues Tyr866, Arg867, and Lys868 of helix II, His874, Asp876, Lys877, Thr879, and Gln881 of the HPD loop, and Phe891, Asn895, Asp896, and Asn903 of helix III. The conservative residues Tyr866, Arg867, Lys868, His874, Asp876, Lys877, and Phe891 were also found in a previous study to be indispensable to the catalytic activity of the DnaJ J domain and the binding of it with the NBD of DnaK. The in silico identification of the importance of auxilin residues Asn895, Asp896, and Asn903 agrees with previous mutagenesis and NMR data suggesting that helix III of the J domain of the T antigen interacts with Hsp70. Furthermore, our data indicate that Thr879 and Gln881 from the HPD loop are also important as they mediate the interaction between the bovine auxilin J domain and Hsc70.
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影响因子：
14.9
作者：
Schneidman-Duhovny D;Inbar Y;Nussinov R;Wolfson HJ
通讯作者：
Wolfson HJ
影响因子：
5.8
作者：
Pronk, Sander;Pall, Szilard;Lindahl, Erik
通讯作者：
Lindahl, Erik
DOI：
10.1007/s00249-010-0638-3
发表时间：
2011-02-01
影响因子：
2
作者：
Kalikka, Janne;Akola, Jaakko
通讯作者：
Akola, Jaakko
DOI：
10.1073/pnas.042670999
发表时间：
2002-02-19
影响因子：
11.1
作者：
Fewell, SW;Pipas, JM;Brodsky, JL
通讯作者：
Brodsky, JL
影响因子：
2.8
作者：
Jilong Zhang;Qingchuan Zheng;Hong-Xing Zhang
通讯作者：
Jilong Zhang;Qingchuan Zheng;Hong-Xing Zhang