Int. J. Dev. Biol. 50: 341 - 358 (2006)
doi: 10.1387/ijdb.052063jt
© UPV/EHU Press

The evolution of the structure of tubulin and its potential consequences for the role and function of microtubules in cells and embryos

Jack A. Tuszynski1,*, Eric J. Carpenter1, J. Torin Huzil1, Wojtek Malinski1, Tyler Luchko1 and Richard F. Luduena2

1Department of Physics, University of Alberta, Edmonton, Alberta, Canada and 2Department of Biochemistry, MSC 7760, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA

ABSTRACT This paper discusses the results of homology modeling and resulting calculation of key structural and physical properties for close to 300 tubulin sequences, including alpha, beta, gamma, delta and epsilon -tubulins. The basis for our calculations was the structure of the tubulin dimer published several years ago by Nogales et al. (1998), later refined to 3.5 Å resolution by Löwe et al. (2001). While, it appears that the alpha, beta and gamma-tubulins segregate into distinct structural families, we have found several differences in the physical properties within each group. Each of the alpha, beta and gamma- tubulin groups exhibit major differences in their net electric charge, dipole moments and dipole vector orientations. These properties could influence functional characteristics such as microtubule stability and assembly kinetics, due to their effects on the strength of protein-protein interactions. In addition to the general structural trends between tubulin isoforms, we have observed that the carboxy-termini of alpha and beta-tubulin exists in at least two stable configurations, either projecting away from the tubulin (or microtubule) surface, or collapsed onto the surface. In the latter case, the carboxy-termini form a lattice distinctly different from that of the well-known A and B lattices formed by the tubulin subunits. However, this C-terminal lattice is indistinguishable from the lattice formed when the microtubule-associated protein tau binds to the microtubule surface. Finally, we have discussed how tubulin sequence diversity arose in evolution giving rise to its particular phylogeny and how it may be used in cell- and tissue-specific expression including embryonal development.

Keywords:

tubulin, microtubule, isoform, homology model, dipole

*Corresponding author e-mail: jtus@phys.ualberta.ca