Tubulin folding cofactors as GTPase-activating proteins. GTP hydrolysis and the assembly of the alpha/beta-tubulin heterodimer.
In vivo, many proteins must interact with molecular chaperones to attain their native conformation. In the case of tubulin, newly synthesized alpha- and beta-subunits are partially folded by cytosolic chaperonin, a double-toroidal ATPase with homologs in all kingdoms of life and in most cellular compartments. alpha- and beta-tubulin folding intermediates are then brought together by tubulin-specific chaperone proteins (named cofactors A-E) in a cofactor-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 beta-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 cofactors behave as GTPase-activating proteins, stimulating the GTP-binding protein beta-tubulin to hydrolyze its GTP.
Tian
G
G
Department of Biochemistry, New York University Medical Center, New York, New York 10016, USA.
Bhamidipati
A
A
Cowan
N J
NJ
Lewis
S A
SA
D001665:Binding Sites; D019281:Dimerization; D020690:GTPase-Activating Proteins; D006160:Guanosine Triphosphate / Q000378:metabolism*; D006868:Hydrolysis; D017510:Protein Folding; D011506:Proteins / Q000502:physiology*; D014404:Tubulin / Q000737:chemistry*
D020690:GTPase-Activating Proteins; D011506:Proteins; D014404:Tubulin; D006160:Guanosine Triphosphate