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J Biol Chem, Vol. 273, Issue 37, 23645-23648, September 11, 1998
-HELICAL PROPENSITIES OF THE AMINO ACIDS IN NON-POLAR
ENVIRONMENTS
From Structural Biology and Biochemistry, Research Institute,
Hospital for Sick Children, Toronto, Ontario M5G 1X8 and the
Department of Biochemistry, University of Toronto, Toronto,
Ontario M5S 1A8, Canada
Although the chains of amino acids in proteins
that span the membrane are demonstrably helical and hydrophobic, little
attention has been paid toward addressing the range of helical
propensities of individual amino acids in the non-polar environment of
membranes. Because it is inappropriate to apply soluble protein-based
structure prediction algorithms to membrane proteins, we have used
de novo designed peptides
(KKAAAXAAAAAXAAWAAXAAAKKKK-amide,
where X indicates one of the 20 commonly occurring amino
acids) that mimic a protein membrane-spanning domain to determine the
-helical proclivity of each residue in the isotropic non-polar
environment of n-butanol. Peptide helicities measured by
circular dichroism spectroscopy were found to range from
222 =
17,000 ° (Pro) to
38,800 ° (Ile) in
n-butanol. The relative helicity of each amino acid is
shown to be well correlated with its occurrence frequency in natural transmembrane segments, indicating that the helical propensity of
individual residues in concert with their hydrophobicity may be a key
determinant of the conformations of protein segments in membranes.
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