Ja. Zitzewitz et al., Preformed secondary structure drives the association reaction of GCN4-p1, a model coiled-coil system, J MOL BIOL, 296(4), 2000, pp. 1105-1116
The structure of the transition state for the rate-limiting step in the fol
ding and association of the homodimeric coiled-coil peptide GCN4-p1, was pr
obed by mutational analysis. A series of quadruple amino acid replacements
that spanned the helix propensity scale were made at the four external f po
sitions in the heptad repeat. Equilibrium and kinetic circular dichroism st
udies demonstrate that both the stability and the unfolding and refolding r
ate constants vary with helix propensity but also reflect interactions of t
he altered side-chains with their local environments. Pairwise replacements
and fragment studies show that the two C-terminal heptads are the likely s
ource of the nucleating helices. Helix-helix recognition between preformed
elements of secondary structure plays an important role in this fundamental
folding reaction. (C) 2000 Academic Press.