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Updated: Feb 16, 2026
07:51
Pull-down of Calmodulin-binding Proteins
Published on: January 23, 2012
26.0K
Calmodulin fishing with a structurally disordered bait triggers CyaA catalysis
Darragh P O'Brien1, Dominique Durand2, Alexis Voegele1
1Institut Pasteur, UMR CNRS 3528, Chemistry and Structural Biology Department, Paris, France.
Plos Biology
|December 30, 2017
Summary
The adenylate cyclase toxin (AC) from Bordetella pertussis becomes highly active when calmodulin binds, transitioning from a disordered state to a stable, ordered structure. This CaM binding enhances AC
Area of Science:
- Biochemistry
- Molecular Biology
- Structural Biology
Background:
- Adenylate cyclase toxin (CyaA) from Bordetella pertussis is a key virulence factor.
- Its catalytic domain (AC) is activated by calmodulin (CaM) in the host cytosol, producing high cAMP levels and inducing cell death.
Purpose of the Study:
- To elucidate the structural mechanisms underlying CaM-mediated activation of the AC catalytic domain.
- To understand how CaM binding influences the enzyme's structure and catalytic activity.
Main Methods:
- Small-angle X-ray scattering (SAXS)
- Hydrogen/deuterium exchange mass spectrometry (HDX-MS)
- Synchrotron radiation circular dichroism (SR-CD)
Main Results:
- AC exhibits significant structural disorder in the absence of CaM.
- CaM binding induces a disorder-to-order transition in a 75-residue segment of AC.
- CaM binding causes long-range allosteric effects, stabilizing the catalytic site while maintaining catalytic loop flexibility.
Conclusions:
- The high enzymatic activity of AC results from a balance between CaM-induced stabilization and preserved catalytic loop flexibility.
- CaM-induced reduction of conformational disorder in AC may be relevant to other CaM-activated enzymes.
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