Extracting information on folding from the amino acid sequence: consensus regions with preferred conformation in homologous proteins.

TitleExtracting information on folding from the amino acid sequence: consensus regions with preferred conformation in homologous proteins.
Publication TypeJournal Article
Year of Publication1992
AuthorsRooman, M. J., and Wodak S. J.
JournalBiochemistry
Volume31
Issue42
Pagination10239-49
Date Published1992 Oct 27
ISSN0006-2960
KeywordsAdenylate Kinase, Alcohol Dehydrogenase, Amino Acid Sequence, Animals, Cytochrome c Group, Globins, Hemoglobins, Humans, Macromolecular Substances, Models, Molecular, Molecular Sequence Data, Muramidase, Myoglobin, Plastocyanin, Protein Conformation, Protein Folding, Proteins, Ribonucleases, Sequence Homology, Amino Acid, Thermolysin
Abstract

It is investigated whether protein segments predicted to have a well-defined conformational preference in the absence of tertiary interactions are conserved in families of homologous proteins. The prediction method follows the procedures of Rooman, M., Kocher, J.-P., and Wodak, S. (preceding paper in this issue). It uses a knowledge-based force field that incorporates only local interactions along the sequence and identifies segments whose lowest energy structure displays a sizable energy gap relative to other computed conformations. In 13 of the protein families and subfamilies considered that are sufficiently homologous to have similar 3D structures, at least one region is consistently predicted as having the same preferred conformation in virtually all family members. These regions are between 4 and 26 residues long. They are often located at chain ends and correspond primarily to segments of secondary structure heavily involved in interactions with the rest of the protein, suggesting that they could act as nuclei around which other parts of the structure would assemble. Experimental data on early folding intermediates or on protein fragments with appreciable structure in aqueous solution are available for more than half of the protein families. Comparison of our results with these data is quite favorable. They reveal that each of the experimentally identified early formed, or independently stable, substructures harbors at least one of the segments consistently predicted as having a preferred conformation by our procedure. The implications of our findings for the conservation of folding pathways in homologous proteins are discussed.

Alternate JournalBiochemistry
PubMed ID1329944