A hydrophobic folding unit
cutting procedure originally developed
for dissecting single-chain proteins, has been applied to a dataset of
dissimilar two-chain
protein-protein interfaces.
Rather than consider each
individual chain separately, the two-chain complex has been treated as a single
chain. Hence, the two-chain complex is viewed as a single-chain protein folding
problem. The two-chain parsing results provide strong support for the scheme
where by protein folding involves first a process of independent collapse of
hydrophobic folding units, followed by their association. In analogy to the
protein folding process, the two-state model complex, involving cooperative
folding of the two chains in the complex, corresponds to the first step in
protein folding, where compact, hydrophobic nuclei are formed. On the other
hand, the three-state model complex, involving binding of the already folded
monomers, relates to the association of the hydrophobic folding units within a
single chain. Furthermore, compactness and hydrophobicity are shown to play a
critical role in the first, two-state model protein-protein complex case, as
well as in protein folding. The similarity between folding entities in protein
cores and in protein-protein interfaces, despite the absence of some chain
connectivities in the latter, indicates that chain linkage does not necessarily
affect the native conformation. It further substantiates the notion that
tertiary, non-local interactions play a critical role in the formation of
folding nuclei. These compact, hydrophobic, two-chain folding units, derived
from structurally dissimilar protein-protein interfaces, provide a set of data
useful for defining folding nuclei.
An example : 1bsrAB being cut into two units :
Click on image to view in full scale.
Please send questions or suggestions to
tsai@protein3d.ncifcrf.gov
Jan 28, 1997
