Structural basis for the interaction of tubulin with proteins and drugs that affect microtubule dynamics.
The microtubule cytoskeleton is a highly regulated system. At different times in the cell cycle and positions within the organism, microtubules can be very stable or highly dynamic. Stability and dynamics are regulated by interaction with a large number of proteins that themselves may change at specific points in the cell cycle. Exogenous ligands can disrupt the normal processes by either increasing or decreasing microtubule stability and inhibiting their dynamic behavior. The recent determination of the structure of tubulin, the main component of microtubules, makes it possible now to begin to understand the details of these interactions. We review here the structure of the tubulin dimer, with particular regard to how proteins and drugs may bind and modulate microtubule dynamics.
Downing
K H
KH
Donner Laboratory, Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA. khdowning@lbl.gov
D000470:Alkaloids / Q000378:metabolism*; D000818:Animals; D003078:Colchicine / Q000378:metabolism; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D017239:Paclitaxel / Q000378:metabolism; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism*; D014747:Vinblastine / Q000378:metabolism
D000470:Alkaloids; D008869:Microtubule-Associated Proteins; D014404:Tubulin; D014747:Vinblastine; D017239:Paclitaxel; D003078:Colchicine