How the PH Domain in ASAP1 Activates GTP Hydrolysis
Author Information
Author(s): Soubias Olivier, Foley Samuel L., Jian Xiaoying, Jackson Rebekah A., Zhang Yue, Rosenberg Eric M. Jr, Li Jess, Heinrich Frank, Johnson Margaret E., Sodt Alexander J., Randazzo Paul A., Byrd R. Andrew
Primary Institution: Center for Structural Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA
Hypothesis
The PH domain of ASAP1 enhances its catalytic activity through an allosteric mechanism.
Conclusion
The PH domain of ASAP1 significantly increases the rate of GTP hydrolysis by facilitating substrate binding and inducing conformational changes.
Supporting Evidence
- The PH domain enhances the catalytic activity of ASAP1 by binding to Arf·GTP.
- Membrane recruitment by the PH domain increases the effective concentration of the substrate.
- The study provides the first quantitative analysis of the contribution of the PH domain to catalytic activation.
- Mutations in the PH domain significantly affect its ability to activate GTP hydrolysis.
Takeaway
The PH domain helps a protein called ASAP1 work better by making it stick to the right spot and changing its shape to do its job faster.
Methodology
The study used Nuclear Magnetic Resonance (NMR), Molecular Dynamics (MD) simulations, and mathematical modeling to analyze the interaction between ASAP1 and Arf1.
Digital Object Identifier (DOI)
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