Biophysical and Computational Studies of Membrane Penetration by the GRP1 Pleckstrin Homology Domain
2011

Studying How GRP1-PH Domain Interacts with Membranes

publication Evidence: moderate

Author Information

Author(s): Lumb Craig N., He Ju, Xue Yi, Stansfeld Phillip J., Stahelin Robert V., Kutateladze Tatiana G., Sansom Mark S.P.

Primary Institution: Department of Biochemistry, University of Oxford

Hypothesis

The study investigates the interaction between the GRP1 pleckstrin homology domain and the lipid bilayer, focusing on specific and nonspecific interactions.

Conclusion

The GRP1-PH domain penetrates the membrane and interacts with lipids through a dual-recognition mechanism involving both specific and nonspecific contacts.

Supporting Evidence

  • MD simulations showed that GRP1-PH interacts with surrounding lipids in addition to PI(3,4,5)P3.
  • NMR data indicated significant changes in chemical shifts in loop regions upon binding to PI(3,4,5)P3.
  • Monolayer penetration experiments demonstrated that mutations in hydrophobic residues reduced membrane penetration.

Takeaway

This study looks at how a protein called GRP1-PH sticks to cell membranes and how it interacts with the fats in those membranes.

Methodology

The study used molecular dynamics simulations, NMR spectroscopy, and monolayer penetration experiments to analyze the interactions of GRP1-PH with membranes.

Limitations

The initial structure used for simulations may not fully represent the membrane-bound conformation of GRP1-PH.

Digital Object Identifier (DOI)

10.1016/j.str.2011.04.010

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