PATHWAY LEADING TO CORRECTLY FOLDED BETA-TUBULIN

We describe the complete beta-tubulin folding pathway. Folding interme diates produced via ATP-dependent interaction with cytosolic chaperoni n undergo a sequence of interactions with four proteins (cofactors A, D, E, and C). The postchaperonin steps in the reaction cascade do not depend on ATP or GTP hydrolysis, although GTP plays a structural role in tubulin folding. Cofactors A and D function by capturing and stabil izing beta-tubulin in a quasi-native conformation. Cofactor E binds to the cofactor D-beta-tubulin complex; interaction with cofactor C then causes the release of beta-tubulin polypeptides that are committed to the native state. Sequence analysis identifies yeast homologs of cofa ctors D (cin1) and E (pac2), characterized by mutations that affect mi crotubule function.