Yk. Mok et al., THE DIMERIC DNA-BINDING DOMAIN OF THE HUMAN PAPILLOMAVIRUS E2 PROTEINFOLDS THROUGH A MONOMERIC INTERMEDIATE WHICH CANNOT BE NATIVE-LIKE, Nature structural biology, 3(8), 1996, pp. 711-717
The dimeric DNA binding domain of the human papillomavirus E2 protein
displays a two-state concerted unfolding and dissociation, with no det
ectable monomeric intermediate species accumulated at equilibrium. We
investigated the kinetic folding mechanism of the dimeric domain using
stopped-flow spectroscopic techniques and observed a fast forming mon
omeric intermediate, followed by a slower bimolecular reaction. Both p
hases involve secondary structure rearrangements of similar magnitude.
Our results support a folding pathway in which the formation of an ea
rly monomeric intermediate, with characteristics of hydrophobic collap
se, is followed by a bimolecular step encompassing association and fol
ding. The interwoven folding topology of this particular type of dimer
ic P-barrel found in the E2 DNA binding domain strongly suggests that
any monomeric species formed could not be native-like.