The making and breaking of microtubules ( found that in GDP-bound tubulin the co...)

The making and breaking of microtubules

found that in GDP-bound tubulin, the contacts between the alpha and beta tubulins within and between dimers are both affected, although in significantly different ways, resulting in a curved protofilament that cannot form lateral contacts.

By contrast, in tubulin that binds the GTP analogue GMPCPP, contacts between the subunits are straight enough to allow lateral interaction between growing protofilaments. Says Nogales, "Such contacts appear semiconserved with respect of those previously seen in microtubules, and suggest a mechanism by which microtubules will first grow into open sheets that are able to quickly 'zip' into a close tube."

Interestingly, in both polymerizing and depolymerizing transitional states, protofilaments usually occur in pairs. This is puzzling, because the most common microtubule has 13 protofilaments, which points to a change in the number of protofilaments after GTP hydrolysis, by a mechanism not yet understood.

The new high-resolution models of tubulin transitional states will be used to understand how microtubules explore their cellular environment to find their goals -- a process crucial to the accurate deployment of spindles during cell division, for example -- and how drugs can be designed and targeted to put a monkey wrench into the growth of cancer cells.

"Nucleotide-dependent bending flexibility of tubulin regulates microtubule assembly," by Hong-Wei Wang and Eva Nogales, appears in the 16 June 2005 issue of Nature.

Source:DOE/Lawrence Berkeley National Laboratory

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( found that in GDP-bound tubulin the co...)The making and breaking of microtubules