Related Experiment Videos
Pathway for large-scale conformational change in annexin V
J Sopkova-De Oliveira Santos1, S Fischer, C Guilbert
1Section de Biophysique des Protéines et des Membranes, Département de Biologie Cellulaire et Moléculaire, CEA-Saclay, 91191 Gif-sur-Yvette Cedex, France.
Biochemistry
|November 23, 2000
Summary
Calcium binding to annexin V domain III causes significant conformational changes, exposing Trp187. Computer simulations reveal this involves increased strain and helix unwinding, guided by acidic residues.
Area of Science:
- Biochemistry
- Structural Biology
- Computational Biology
Background:
- Annexin V is a calcium-dependent phospholipid-binding protein.
- Crystallography indicates calcium binding to domain III of annexin V induces a conformational change with Trp187 exposure.
Purpose of the Study:
- To computationally investigate the conformational transition of annexin V domain III upon calcium binding.
- To elucidate the molecular mechanisms and energy landscape of this transition.
Main Methods:
- Molecular dynamics simulations were employed.
- The conjugate peak refinement method was used to determine the low-energy pathway.
- Solvent effects were incorporated using nonuniform charge scaling.
Main Results:
- The conformational change involves significant strain and helix unwinding (>300 dihedral angle transitions).
- Improved protein-protein interaction energies compensate for the increased strain.
- Acidic residues directly interact with the indole ring of Trp187 throughout the pathway.
Conclusions:
- The study provides a detailed molecular mechanism for annexin V conformational change.
- Acidic residues are crucial in mediating the transition via interactions with Trp187.
- The findings align with experimental data on pH, calcium, and mutational effects.