3. (4pts each) Suppose you expose cells to drugs with the following effects. Wil

Question

3. (4pts each) Suppose you expose cells to drugs with the following effects. Will these tend to promote microtubule growth, shrinkage, or neither? Please provide a brief explanation. A. The drug inhibits the exchange of GTP into and GDP out of free tubulin dimers. B. The drug inhibits hydrolysis of the GTP bound to tubulin in microtubules. C. The drug increases the affinity of tubulin dimers carrying GTP for other tubulin dimers. D. The drug increases the affinity of tubulin dimers carrying GDP for other tubulin dimers. E. The drug increases the affinity of alpha and beta tubulin monomers for each other within tubulin dimers.

Explanation / Answer

Microtubules are composed of a single type of globular protein, called tubulin. Tubulin is a dimer consisting of two polypeptides, -tubulin and -tubulin.

Tubulin dimers can depolymerize as well as polymerize, and microtubules can undergo rapid cycles of assembly and disassembly. Both - and -tubulin bind GTP. The GTP bound to -tubulin (though not that bound to -tubulin) is hydrolyzed to GDP after its polymerisation.

This GTP hydrolysis weakens the binding affinity of tubulin for adjacent molecules, thereby favoring depolymerization.

A. The drug that inhibits the exchange of GTP into and GDP out of free tubulin dimers will halt the microtubule growth as the tubulin dimers will not be able to exchange the GDP to GTP and without bound GTP, the tubulin dimers cannot polymerise.

B. The drug that inhibits the hydrolysis of GTP bound to tubulin in microtubules will result in stabilization of microtubule. If the GTP is not hydrolysed, the tubulin dimers will not dissocite from the microtubule.

C. The drug increases the affinity of tubulin dimers carrying GTP for other tubulin dimers will have no effect on microtubule growth or shrinkage, as the tubulin dimers has affinity for each other when GTP is bound to them. It is the hydrolysis of GTP molecule which lowers the affinity of tubulin dimers and cause shrinkage.

D. The drug increases the affinity of tubulin dimers carrying GDP for other tubulin dimers will cause microtubule stabilisation. Because when the GTP bound to tubulin is hydrolysed, the affinity of tubulin dimers for adjecent tubulin molecules. So it will effect the shrinkage of microtubules.

E. The drug increasing the affinity of alpha and beta tubulin monomers for each other within tubulin dimer will has no effect on growth or shrinkage. The two monomers of tubulin remein in dimeric form in the microtubule and work as a unit, so increasing their affinity for each other will not cause any effect on microtubule assembly.

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