  The microtubule assembly process has been extensively studied, but the
underlying molecular mechanism remains poorly understood. The structure of an
artificially generated sheet polymer that alternates two types of lateral
contacts and that directly converts into microtubules, has been proposed to
correspond to the intermediate sheet structure observed during microtubule
assembly. We have studied the self-assembly process of GMPCPP tubulins into
sheet and microtubule structures using thermodynamic analysis and stochastic
simulations. With the novel assumptions that tubulins can laterally interact in
two different forms, and allosterically affect neighboring lateral
interactions, we can explain existing experimental observations. At low
temperature, the allosteric effect results in the observed sheet structure with
alternating lateral interactions as the thermodynamically most stable form. At
normal microtubule assembly temperature, our work indicates that a class of
sheet structures resembling those observed at low temperature is transiently
trapped as an intermediate during the assembly process. This work may shed
light on the tubulin molecular interactions, and the role of sheet formation
during microtubule assembly.
