B. Nolting, STRUCTURAL RESOLUTION OF THE FOLDING PATHWAY OF A PROTEIN BY CORRELATION OF PHI-VALUES WITH INTER-RESIDUE CONTACTS, Journal of theoretical biology, 194(3), 1998, pp. 419-428
Folding of barstar, the 10 kDalton inhibitor of the ribonuclease barna
se, has been suggested to follow a nucleation-condensation model [Nolt
ing, B., Golbik, R., Neira, J. L., Soler-Gonzalez, A. S., Schreiber, G
. & Fersht, A. R. (1997). Proc. Nat. Acad. Sci. U.S.A. 94, 826-830], w
here structure growth starts in a particular region of the molecule, t
he folding nucleus. Here the structure of the diffuse nucleus and its
growth in three stages, 500 mu s, 1 ms and 100 ms after initiation of
the folding reaction, is mapped out by using phi-values which are corr
elated with inter-residue contact plots. Barstar folding is initiated
by a significant consolidation of interactions in and around the stran
d(1)-loop(1)-helix(1) motif in the microsecond time scale, followed by
the consolidation of helix(4), which is located close to the C-termin
us and does not have significant residual structure in the cold-denatu
red state. The non-uniform structure consolidation is most pronounced
in the early stages of folding. The late folding events of barstar are
characterized by a propagation of structure consolidation from the Na
nd C-termini towards residues located in the center of the sequence. (
C) 1998 Academic Press.