The self-assembly of globular proteins is often portrayed as a nucleation process in which the hydrogen bonding in segments of secondary structure is the precondition for further folding. We show here that this concept is unlikely because both the buried interior regions and the peptide chain turns of the folded protein (i.e., inside and outside) are predicted solely by the hydrophobicity of the residues, taken in sequential order along the chain. The helices and strands span the protein, and this observed secondary structure is seen to coincide with the regions predicted to be buried from hydrophobicity considerations alone. Our evidence suggests that linear chain regions rich in hydrophobic residues serve as small clusters that fold against each other, with concomitant or even later fixation of secondary structure. A helix or strand would arise in this folding process as one of a few energetically favorable alternatives for a given cluster, followed by a shift in the equilibrium between secondary structure conformers upon cluster association. the linera chain hydrophobicity alternates between locally maximal and minimal values, and these extrema partition the polypeptide chain into structural segments. This partitioning is seen in the x-ray structure as isodirectional segments bracketed between peptide chain-turns, with the segments expressed most often as helices and strands. the segment interactions define the geometry of the molecular interior and the chain-turns describe the predominant features of the molecular coastline. The segmentation of the molecule by linear chain hydrophobicity imposes a major geometric constraint upon possible folding events.
|Original language||English (US)|
|Number of pages||5|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - Aug 1980|
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