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Ca2+-bound calmodulin forms a compact globular structure on binding four trifluoperazine molecules in solution.
N Matsushima1, N Hayashi, Y Jinbo
1Department of Biophysics, School of Health Sciences, Sapporo Medical University, Sapporo, Hokkaido 060-8556, Japan. matusima@shs.sapmed.ac.jp
The Biochemical Journal
|March 23, 2000
Summary
Small-angle X-ray scattering reveals how calmodulin (CaM) changes shape when binding trifluoperazine (TFP). Ca(2+)-bound CaM becomes more compact with TFP, even without Ca(2+).
Area of Science:
- Biochemistry
- Structural Biology
- Biophysics
Background:
- Calmodulin (CaM) is a crucial calcium-binding protein involved in cellular signaling.
- Previous studies using Small-angle X-ray scattering (SAXS) showed CaM adopts a compact globular shape upon binding two molecules of N-(6-aminohexyl)-5-chloro-1-naphthalenesulphonamide (W-7).
Purpose of the Study:
- To investigate the conformational changes of calmodulin (CaM) upon binding to the antagonist trifluoperazine (TFP).
- To determine the effect of Ca(2+) presence or absence on TFP-induced CaM structural alterations.
Main Methods:
- Small-angle X-ray scattering (SAXS) was employed to analyze CaM structure.
- SAXS measurements were performed on CaM in solution with and without Ca(2+) and in the presence of TFP.
Main Results:
- Binding of four TFP molecules to Ca(2+)-saturated CaM resulted in a highly compact globular shape, consistent with previously observed CaM-W-7 complexes.
- Ca(2+)-free CaM also exhibited conformational changes upon TFP binding, leading to a slightly reduced radius of gyration (R(g)) compared to Ca(2+)-free CaM alone.
Conclusions:
- Trifluoperazine binding induces significant conformational changes in calmodulin, promoting a more compact structure.
- The presence of Ca(2+) enhances the TFP-induced compaction of CaM, but TFP can also alter CaM conformation in a Ca(2+)-independent manner.