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Highly restricted distributions of hydrophobic and charged amino acids in longitudinal quadrants of alpha-helices.

1991; Elsevier BV; Volume: 266; Issue: 9 Linguagem: Inglês

10.1016/s0021-9258(19)67625-8

1083-351X

Rochelle R. Torgerson, R A Lew, V E Reyes, Larry W. Hardy, Robert E. Humphreys,

Amino Acid Enzymes and Metabolism

Helix formation in folding proteins is stabilized by binding of recurrent hydrophobic side chains in one longitudinal quadrant against the locally most hydrophobic region of the protein.To test this hypothesis, we fitted sequences of 247 a-helices of 55 proteins to the circular (infinite) template OOAOOOOOOAOOOOOOAO to maximize the strip-of-helix hydrophobicity index (the mean hydrophobicity of residues in 0 positions).These templatepredicted configurations closely matched crystallographic structures in 87% of four-or five-turn helices compared.We determined the longitudinal quadrant distributions of amino acids in the template-fitted, sheet projections of a-helices with respect to the best longitudinal, hydrophobic strip on each helix and to the N and C termini, interiors, and entire helices.Amino acids Leu, Ile, Val, and Phe were concentrated in one longitudinal quadrant ( p < 0.001).Lys, Arg, Asp, and Glu were not in the quadrant of Leu, Ile, Val, and Phe ( p c 0.001).Significant quadrant distributions for other amino acids and for termini of the helices were also found.a-Helices in proteins are predicted with sensitivity and efficiency from runs of aliphatic, hydrophobic amino acids only at recurrent positions (n, n + 4, n + 7, n + 11, n + 14, etc.) that form an axial hydrophobic strip when the subsequence is coiled as an a-helix (1).Perutz et al. (2) originally observed in the a-helices of hemoglobin the recurrence of invariant, nonpolar residues every 3.6 residues, on the average, making the interior faces of the helices nonpolar.Schiffer and Edmundson (3) created the wheel projection to identify such segments with helical potential.Eisenberg et al. (4) and Finer-Moore and Stroud (5) developed methods based upon amphipathic moments to predict a-helices.Kaiser and Taylor (6) tested the function of a longitudinal hydrophobic surface on a-helices to promote folding against a hydrophobic surface.