Modeling Signal Propagation Mechanisms and Ligand-Based Conformational Dynamics of the Hsp90 Molecular Chaperone Full-Length Dimer
2009

Understanding Hsp90 Dynamics and Signal Propagation Mechanisms

publication Evidence: high

Author Information

Author(s): Giulia Morra, Gennady Verkhivker, Giorgio Colombo

Primary Institution: Istituto di Chimica del Riconoscimento Molecolare, Consiglio Nazionale delle Ricerche, Milano, Italy

Hypothesis

The study investigates how ligand binding affects the conformational dynamics and signal propagation in the Hsp90 molecular chaperone.

Conclusion

The results reveal that ATP binding stabilizes a closed conformation of Hsp90, while ADP binding leads to an open conformation, affecting inter-domain communication.

Supporting Evidence

  • ATP binding induces a closing motion stabilizing N-terminal dimerization.
  • ADP binding leads to a more open, relaxed state of Hsp90.
  • Different ligand binding affects the communication pathways between Hsp90 domains.

Takeaway

Hsp90 is like a helper protein that changes shape when it binds to different molecules, which helps it do its job better.

Methodology

The study used molecular dynamics simulations to analyze the conformational changes of Hsp90 in different ligand-bound states.

Limitations

The simulations may not have been long enough to observe complete opening of the ATP-lid in the ADP-bound or apo structures.

Digital Object Identifier (DOI)

10.1371/journal.pcbi.1000323

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