Journal of Molecular Modeling

, 23:320 | Cite as

Steered molecular dynamics simulation of the binding of the bovine auxilin J domain to the Hsc70 nucleotide-binding domain

  • You-Lin Xue
  • Lei Zhou
  • Yuna Sun
  • Hui Li
  • Gary W. Jones
  • Youtao SongEmail author
Original Paper


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.


Steered molecular dynamics Bovine auxilin Jdomain Hsc70 nucleotide-binding domain Protein–protein interactions 



This work was supported by the National Natural Science Foundation of China under grant nos. 31570154 and 31201285, the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry of China under grant no. 2013693; and Grants for Distinguished Professors of Liaoning Province and the General Project of the Education Department of Liaoning Province, China under grant no. L2014009.

Supplementary material

894_2017_3453_MOESM1_ESM.docx (31 kb)
Table S1 (DOCX 31 kb)
894_2017_3453_MOESM2_ESM.docx (1 mb)
Fig. S1 (DOCX 1028 kb)


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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • You-Lin Xue
    • 1
    • 2
  • Lei Zhou
    • 1
  • Yuna Sun
    • 3
  • Hui Li
    • 3
  • Gary W. Jones
    • 4
  • Youtao Song
    • 1
    • 3
    Email author
  1. 1.School of Environmental ScienceLiaoning UniversityShenyangChina
  2. 2.College of Light IndustryLiaoning UniversityShenyangChina
  3. 3.Province Key Laboratory of Animal Resource and Epidemic Disease Prevention, College of Life ScienceLiaoning UniversityShenyangChina
  4. 4.Centre for Biomedical Science Research, School of Clinical and Applied SciencesLeeds Beckett UniversityLeedsUK

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