Differential colchicine-binding across eukaryotic families: The role of highly conserved Pro268 beta and Ala248 beta residues in animal tubulin

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 Pro268 beta and Ala248 beta (270 beta and 250 beta 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. (C) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved