Spectrin: an alternate target for cytoskeletal drugs

Abstract

Cytoskeletal drugs having enormous therapeutic potential act on the cytoskeletal components like actin, tubulin either by promoting polymerization or destabilizing the same. Here we present the interaction of the popular cytoskeletal drugs such as taxol, latrunculin and cytochalasin with spectrin, a huge protein with multi domains that forms the cytoskeletal network. Particularly, the actin binding domain of spectrin regulates the dynamics of the actin cytoskeleton. We followed the binding of these drugs to its actin binding domain and intact spectrin as well. These drugs bind with moderate affinity (K_b ∼ 10⁴ M⁻¹) and the interaction with actin binding domain is entropy driven and hydrophobic in nature as determined by Van’t Hoff plot. The docking studies and molecular dynamics simulations further corroborate the experimental findings. Particularly the higher binding constants in the case of latrunculin and cytochalasin to the actin binding domain of spectrin suggest the binding sites are presumably located in its actin binding domain.

Communicated by Ramaswamy H. Sarma

Keywords:

• Spectrin
• actin binding domain
• cytoskeletal drugs
• taxol
• cytochalasin
• latrunculin

Acknowledgement

SD acknowledges the funding from Department of Science and Technology, Women Scientists scheme (WOS-A), Government of India. We also thank of Saha Institute of Nuclear Physics for infrastructural facilities. We are grateful to Prof. Swagata Dasgupta’s laboratory, Indian Institute of Technology Kharagpur for providing the access to NACESS.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

The work was supported by the Department of Science and Technology (DST), Government of India [grant number SR/WOS-A/LS-173/2016].