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Actin-Curcumin Interaction: Insights into the Mechanism of Actin Polymerization Inhibition

Dhar, Gopa and Chakravarty, Devlina and Hazra, Joyita and Dhar, Jesmita and Poddar, Asim and Pal, Mahadeb and Chakrabarti, Pinak and Surolia, Avadhesha and Bhattacharyya, Bhabatarak (2015) Actin-Curcumin Interaction: Insights into the Mechanism of Actin Polymerization Inhibition. In: BIOCHEMISTRY, 54 (4). pp. 1132-1143.

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Official URL: http://dx.doi.org/ 10.1021/bi5014408


Curcumin, derived from rhizomes of the Curcuma longa plant, is known to possess a wide range of medicinal properties. We have examined the interaction of curcumin with actin and determined their binding and thermodynamic parameters using isothermal titration calorimetry. Curcumin is weakly fluorescent in aqueous solution, and binding to actin enhances fluorescence several fold with a large blue shift in the emission maximum. Curcumin inhibits microfilament formation, which is similar to its role in inhibiting microtubule formation. We synthesized a series of stable curcumin analogues to examine their affinity for actin and their ability to inhibit actin self-assembly. Results show that curcumin is a ligand with two symmetrical halves, each of which possesses no activity individually. Oxazole, pyrazole, and acetyl derivatives are less effective than curcumin at inhibiting actin self-assembly, whereas a benzylidiene derivative is more effective. Cell biology studies suggest that disorganization of the actin network leads to destabilization of filaments in the presence of curcumin. Molecular docking reveals that curcumin binds close to the cytochalasin binding site of actin. Further molecular dynamics studies reveal a possible allosteric effect in which curcumin binding at the barbed end of actin is transmitted to the pointed end, where conformational changes disrupt interactions with the adjacent actin monomer to interrupt filament formation. Finally, the recognition and binding of actin by curcumin is yet another example of its unique ability to target multiple receptors.

Item Type: Journal Article
Additional Information: Copy right for this article belongs to the AMER CHEMICAL SOC, 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Depositing User: Id for Latest eprints
Date Deposited: 23 Mar 2015 09:58
Last Modified: 23 Mar 2015 09:58
URI: http://eprints.iisc.ac.in/id/eprint/51083

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