Gl. Tian et al., QUASI-NATIVE CHAPERONIN-BOUND INTERMEDIATES IN FACILITATED PROTEIN-FOLDING, The Journal of biological chemistry, 270(41), 1995, pp. 23910-23913
Chaperonins are known to facilitate protein folding, but their mechani
sm of action is not well understood. The fact that target proteins are
released from and rebind to different chaperonin molecules (''cycling
'') during a folding reaction suggests that chaperonins function by un
folding aberrantly folded molecules, allowing them multiple opportunit
ies to reach the native state in bulk solution. Here we show that the
cycling of alpha-tubulin by cytosolic chaperonin (c-cpn) can be uncoup
led from the action of cofactors required to complete the folding reac
tion. This results in the accumulation of folding intermediates which
are chaperonin-bound, stable, and quasi-native in that they bind GTP n
onex-changeably. We present evidence that these intermediates can be g
enerated without the target protein leaving c-cpn. These data show tha
t, in contrast to prevailing models, target proteins can maintain, and
possibly acquire, significant native-like structure while chaperonin-
bound.