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Updated: May 28, 2026
07:51
Pull-down of Calmodulin-binding Proteins
Published on: January 23, 2012
Subtle pH differences trigger single residue motions for moderating conformations of calmodulin.
Ali Rana Atilgan1, Ayse Ozlem Aykut, Canan Atilgan
1Faculty of Engineering and Natural Sciences, Sabanci University, 34956 Istanbul, Turkey.
The Journal of Chemical Physics
|October 28, 2011
Summary
Calmodulin (CaM) controls calcium signaling through conformational changes. Perturbation-response scanning reveals residue E31’s crucial role in CaM’s pH-sensitive dynamics and ligand recognition.
Area of Science:
- Biochemistry
- Structural Biology
- Molecular Dynamics
Background:
- Calmodulin (CaM) is a key calcium-binding protein regulating diverse cellular processes.
- Understanding CaM's conformational flexibility is vital for deciphering its signaling mechanisms.
Purpose of the Study:
- To elucidate the ligand recognition mechanisms of calcium-bound CaM.
- To investigate the conformational dynamics of CaM in response to perturbations and pH changes.
Main Methods:
- Utilized perturbation-response scanning (PRS) combined with molecular dynamics simulations.
- Analyzed conformational changes induced by targeted residue perturbations.
- Employed pK(a) calculations to assess residue sensitivity to pH variations.
Main Results:
- Identified specific residue perturbations, particularly at E31, that effectively induce target conformational states.
- Demonstrated that residue E31's ionization state is highly sensitive to physiological pH changes.
- Showcased the flexible linker's role in transducing binding information.
Conclusions:
- CaM's conformational states are controlled by twist-bend motions and influenced by residue ionization.
- Residue E31 plays a critical role in CaM dynamics and pH-dependent conformational transitions.
- Findings provide insights into CaM's role in calcium signaling and ligand binding.
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