Microtubule structure and its stabilisation.
Microtubules are designed to be dynamically unstable. GTP hydrolysis converts an initially stable polymeric structure into an unstable one in which strain at the interfaces between longitudinal neighbours in the helical lattice of subunits is balanced by lateral interactions. However, stability can be modulated by a variety of factors, including associated proteins and a variety of drug molecules. Stabilising drugs such as Taxol and the assembly-promoting repeat motifs of tau protein occupy a special pocket in beta-tubulin. Microtubule destabilizing drugs such as colchicine alter the longitudinal interfaces of the subunits so that they cannot assemble into a microtubule lattice. These mechanisms are discussed in terms of the atomic structure of the protein.
Amos
Linda A
LA
MRC Laboratory of Molecular Biology, Hills Road, Cambridge, UKCB2 2QH. laa@mrc-lmb.cam.ac.uk
D003078:Colchicine / Q000737:chemistry / Q000494:pharmacology; D004355:Drug Stability; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D006868:Hydrolysis; D008870:Microtubules / Q000737:chemistry* / Q000378:metabolism; D004364:Pharmaceutical Preparations; D011487:Protein Conformation; D043823:Taxoids / Q000737:chemistry / Q000494:pharmacology; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism
D004364:Pharmaceutical Preparations; D043823:Taxoids; D016875:tau Proteins; D006160:Guanosine Triphosphate; D003078:Colchicine