Discodermolide interferes with the binding of tau protein to microtubules.
We investigated whether discodermolide, a novel antimitotic agent, affects the binding to microtubules of tau protein repeat motifs. Like taxol, the new drug reduces the proportion of tau that pellets with microtubules. Despite their differing structures, discodermolide, taxol and tau repeats all bind to a site on beta-tubulin that lies within the microtubule lumen and is crucial in controlling microtubule assembly. Low concentrations of tau still bind strongly to the outer surfaces of preformed microtubules when the acidic C-terminal regions of at least six tubulin dimers are available for interaction with each tau molecule; otherwise binding is very weak.
Kar
Santwana
S
MRC Laboratory of Molecular Biology, Hills Rd, Cambridge CB2 2QH, UK.
Florence
Gordon J
GJ
Paterson
Ian
I
Amos
Linda A
LA
D000473:Alkanes; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002219:Carbamates; D066298:In Vitro Techniques; D007783:Lactones / Q000494:pharmacology*; D008870:Microtubules / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D011753:Pyrones; D013552:Swine; D014404:Tubulin / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
D000473:Alkanes; D000970:Antineoplastic Agents; D002219:Carbamates; D007783:Lactones; D011753:Pyrones; D014404:Tubulin; D016875:tau Proteins; C071229:discodermolide