title: Simulations of tubulin sheet polymers as possible structural intermediates in microtubule assembly.
abstract: 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.
authors.affiliation: Program in Genetics, Bioinformatics and Computational Biology, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, United States of America.
authors.forename: Zhanghan
authors.initials: Z
authors.lastname: Wu
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Wang
authors.forename: Weihua
authors.initials: W
authors.lastname: Mu
authors.forename: Zhongcan
authors.initials: Z
authors.lastname: Ouyang
authors.forename: Eva
authors.initials: E
authors.lastname: Nogales
authors.forename: Jianhua
authors.initials: J
authors.lastname: Xing
mesh_terms: D000495:Allosteric Site; D000818:Animals; D003198:Computer Simulation; D019281:Dimerization; D006801:Humans; D007700:Kinetics; D008870:Microtubules / Q000378:metabolism*; D011108:Polymers / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D013269:Stochastic Processes; D013696:Temperature; D013816:Thermodynamics; D014404:Tubulin / Q000737:chemistry*
chemical_list: D011108:Polymers; D014404:Tubulin