Tubulin Folding Cofactors as GTPase-activating Proteins

Abstract

In vivo, many proteins must interact with molecular chaperones to attain their native conformation. In the case of tubulin, newly synthesized-and-subunits are partially folded by cytosolic chaperonin, a double-toroi-dal ATPase with homologs in all kingdoms of life and in most cellular compartments.-and-tubulin folding intermediates are then brought together by tubulin-specific chaperone proteins (named cofactors A-E) in a co-factor-containing supercomplex with GTPase activity. Here we show that tubulin subunit exchange can only occur by passage through this supercomplex, thus defining it as a dimer-making machine. We also show that hydrolysis of GTP by-tubulin in the supercomplex acts as a switch for the release of native tubulin heterodimer. In this folding reaction and in the related reaction of tubulin-folding cofactors with native tubulin, the cofac-tors behave as GTPase-activating proteins, stimulating the GTP-binding protein-tubulin to hydrolyze its GTP.