Protein folding: Looping from hydrophobic nuclei

Protein structure can be viewed as a compact linear array of nearly standar d size closed loops of 25-30 amino acid residues (Berezovsky et al., FEBS L etters 2000; 466: 283-286) irrespective of details of secondary structure. The end-to-end contacts in the loops are likely to be hydrophobic, which is a testable hypothesis. This notion could be verified by direct comparison of the loop maps with Kyte and Doolittle hydropathicity plots. This analysi s reveals that most of the ends of the loops are hydrophobic, indeed. The s ame conclusion is reached on the basis of positional autocorrelation analys is of protein sequences of 23 fully sequenced bacterial genomes. Hydrophobi c residues valine, alanine, glycine, leucine, and isoleucine appear prefere ntially at the 25-30 residues distance one from another. These observations open a new perspective in the understanding of protein structure and foldi ng: a consecutive looping of the polypeptide chain with the loops ending pr imarily at hydrophobic nuclei. (C) 2001 Wiley-Liss, Inc.