The B-ring substituent at C-7 of colchicine and the alpha-C-terminus of tubulin communicate through the "tail-body" interaction

Proteins
Shalmali ChakrabortyB Bhattacharyya

Abstract

The carboxy terminals of alphabeta-tubulins are flexible regions rich in acidic amino acid residues that play an inhibitory role in the polymerization of tubulin to microtubules. We have shown that the binding of colchicine and its B-ring analogs (with C-7 substituents) to tubulin are pH sensitive and have high activation energies. Under identical conditions, the binding of analogs without C-7 substituents is pH independent and has lower activation energy. Beta-C-terminus-truncated tubulin (alphabeta(s)) shows similar pH sensitivity and activation energy to native tubulin (alphabeta). Removal of the C-termini of both subunits of tubulin (alpha(s)beta(s)) or the binding of a basic peptide P2 to the negatively charged alpha-C-terminus of tubulin causes a colchicine-tubulin interaction independent of pH with a low activation energy. Tubulin dimer structure shows that the C-terminal alpha-tail is too far from the colchicine binding site to interact directly with the bound colchicine. Therefore, it is likely that the interaction of the alpha-C-terminus with the main body of tubulin indirectly affects the colchicine-tubulin interaction via conformational changes in the main body. We therefore conclude that in the presence of tail-bod...Continue Reading

References

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Citations

Apr 28, 2007·Medicinal Research Reviews·Bhabatarak BhattacharyyaMithu Banerjee
May 15, 2013·The Plant Journal : for Cell and Molecular Biology·Diego BreviarioLaura Morello
Nov 20, 2014·Parasitology Research·Mariana Potenza, María Teresa Tellez-Iñón
May 8, 2014·Journal of Experimental Botany·Elisabeth Lipka, Sabine Müller

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