A NOVEL COCHAPERONIN THAT MODULATES THE ATPASE ACTIVITY OF CYTOPLASMIC CHAPERONIN

The folding of alpha- and beta-tubulin requires three proteins: the he teromeric TCP-1-containing cytoplasmic chaperonin and two additional p rotein cofactors (A and B). We show that these cofactors participate i n the folding process and do not merely trigger release, since in the presence of Mg-ATP alone, alpha- and beta-tubulin target proteins are discharged from cytoplasmic chaperonin in a nonnative form. Like the p rokaryotic cochaperonin GroES, which interacts with the prototypical E scherichia coli chaperonin GroEL and regulates its ATPase activity, co factor A modulates the ATPase activity of its cognate chaperonin. Howe ver, the sequence of cofactor A derived from a cloned cDNA defines a 1 3-kD polypeptide with no significant homology to other known proteins. Moreover, while GroES functions as a heptameric ring, cofactor A beha ves as a dimer. Thus, cofactor A is a novel cochaperonin that is struc turally unrelated to GroES.