Prefoldin recognition motifs in the nonhomologous proteins of the actin and tubulin families

Nascent actin and tubulin molecules undergo a series of complex interaction s with chaperones and are thereby guided to their native conformation. Thes e cytoskeletal proteins have the initial part of the pathway in common: bot h interact with prefoldin and with the cytosolic chaperonin containing tail less complex polypeptide 1. Little is understood with regard to how these c haperones and, in particular, prefoldin recognize the non-native forms of t hese target proteins. Using mutagenesis, we provide evidence that beta -act in and alpha -tubulin each have two prefoldin interaction sites. The most a mino-terminally located site of both proteins shows striking sequence simil arity, although these proteins are nonhomologous. Very similar motifs are p resent in beta- and gamma -tubulin and in the newly identified prefoldin ta rget protein actin-related protein 1. Actin-related proteins 2 and 3 have r elated motifs, but these have altered charge properties. The latter two pro teins do not bind prefoldin, although we identify them here as target prote ins for the cytosolic chaperonin. Actin fragments containing the two prefol din interaction regions compete efficiently with actin for prefoldin bindin g. In addition, they also compete with tubulins, suggesting that these targ et proteins contact similar prefoldin subunits.