文章基本信息

标题：Tau induces cooperative Taxol binding to microtubules
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作者：Jennifer L. Ross ; Christian D. Santangelo ; Victoria Makrides 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：35
页码：12910-12915
DOI：10.1073/pnas.0402928101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Taxol and tau are two ligands that stabilize the microtubule (MT) lattice. Taxol is an anti-mitotic drug that binds {beta} tubulin in the MT interior. Tau is a MT-associated protein that binds both {alpha} and {beta} tubulin on the MT exterior. Both Taxol and tau reduce MT dynamics and promote tubulin polymerization. Tau alone also acts to bundle, stiffen, and space MTs. A structural study recently suggested that Taxol and tau may interact by binding to the same site. Using fluorescence recovery after photobleaching, we find that tau induces Taxol to bind MTs cooperatively depending on the tau concentration. We develop a model that correctly fits the data in the absence of tau, yields the equilibrium dissociation constant of {approx}2 {micro}M, and determines the escape rate of Taxol through one pore to be 1.7 x 103 (M{middle dot}s)-1. Extension of the model yields a measure of Taxol cooperativity with a Hill coefficient of at least 15 when tau is present at a 1:1 molar ratio with tubulin.