Differential colchicine-binding across eukaryotic families: The role of highly conserved Pro268β and Ala248β residues in animal tubulin

Edited by Michael R. Bubb

Received 1 August 2007; received in revised form 13 September 2007; accepted 18 September 2007. published online 28 September 2007.

Abstract

Colchicine–tubulin interaction, responsible for the disruption of microtubule formation, has immense pharmacological importance but is poorly understood in terms of its biological significance. The interaction is characterized by a marked higher affinity of colchicine for animal tubulins compared to tubulins from plants, fungi and protists. From an analysis of tubulin sequences and colchicine–tubulin crystal structure, we propose that Pro268β and Ala248β (270β and 250β in the crystal structure 1SA0) in animal tubulin are crucial for the observed differential binding. We also suggest that mediated by the binding of endogenous molecules to the colchicine-binding site, microtubule assembly in eukaryotes may be modulated in a family specific manner.

Abbreviations: PBS, primary colchicine-binding site, DC, DAMA-colchicine, EBS, extended colchicine-binding site, PCA, principal component analysis

Keywords: Tubulin, Colchicine, Binding site, Principal component analysis, Proline, Beta-strand

a Department of Biochemistry, Bose Institute, P-1/12 CIT Scheme VIIM, Kolkata 700 054, India

b Bioinformatics Centre, Bose Institute, P-1/12 CIT Scheme VIIM, Kolkata 700 054, India

c Department of Biophysics, Bose Institute, P-1/12 CIT Scheme VIIM, Kolkata 700 054, India

Corresponding author. Fax: +91 33 2355 3886.

PII: S0014-5793(07)01029-0

doi:10.1016/j.febslet.2007.09.047

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