Frequencies of amino acid strings in globular protein sequences indicate suppression of blocks of consecutive hydrophobic residues

Citation
R. Schwartz et al., Frequencies of amino acid strings in globular protein sequences indicate suppression of blocks of consecutive hydrophobic residues, PROTEIN SCI, 10(5), 2001, pp. 1023-1031
Citations number
27
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
PROTEIN SCIENCE
ISSN journal
0961-8368 → ACNP
Volume
10
Issue
5
Year of publication
2001
Pages
1023 - 1031
Database
ISI
SICI code
0961-8368(200105)10:5<1023:FOAASI>2.0.ZU;2-Z
Abstract
Patterns of hydrophobic and hydrophilic residues play a major role in prote in folding and function. Long, predominantly hydrophobic strings of 20-22 a mino acids each are associated with transmembrane helices and have been use d to identify such sequences. Much less attention has been paid to hydropho bic sequences within globular proteins. In prior work on computer simulatio ns of the competition between on-pathway folding and off-pathway aggregate formation, we found that long sequences of consecutive hydrophobic residues promoted aggregation within the model, even controlling for overall hydrop hobic content. We report here on an analysis of the frequencies of differen t lengths of contiguous blocks of hydrophobic residues in a database of ami no acid sequences of proteins of known structure. Sequences of three or mor e consecutive hydrophobic residues are found to be significantly less commo n in actual globular proteins than would be predicted if residues were sele cted independently. The result may reflect selection against long blocks of hydrophobic residues within globular proteins relative to what would be ex pected if residue hydrophobicities were independent of those of nearby resi dues in the sequence.