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Predicting the functional motions of p97 using symmetric normal modes
Hyuntae Na1, Guang Song2,3,4
1Department of Computer Science, Penn State Harrisburg, Middletown, Pennsylvania, 17057.
Proteins
|September 23, 2016
Summary
This study reveals the mechanism of p97 protein unfolding. Using normal mode analysis, researchers found p97 uses a valve-like D2 pore for substrate exit and a shut D1 pore, clarifying its substrate processing mechanism.
Area of Science:
- Biochemistry
- Structural Biology
- Molecular Machines
Background:
- The protein complex p97, belonging to the AAA+ family, has known functions but an unclear unfolding mechanism.
- Understanding p97's mechanism is crucial for comprehending its role in cellular processes.
Purpose of the Study:
- To elucidate the functional mechanism of the p97 protein complex.
- To investigate how p97 performs its unfolding activities at a molecular level.
Main Methods:
- Application of normal mode analysis to the six-fold symmetric p97 molecular machine.
- Selection of axial symmetric normal modes with significant movements at D1 or D2 pore residues.
- Validation of predicted functional motions against experimentally observed conformational changes.
Main Results:
- A venous valve-like mechanism at the D2 pore ensures unidirectional substrate exit.
- The D1 pore remains closed throughout the functional process.
- Substrate entry likely occurs through D1/D2 interface gaps due to the shut D1 pore and one-way D2 traffic.
- p97 employs alternating twisting and pulling actions for substrate removal.
Conclusions:
- The study provides new insights into key, previously controversial steps of p97 function.
- The findings reconcile multiple previous observations regarding p97's mechanism.
- A detailed model for p97's substrate unfolding and processing mechanism is proposed.
