title: Glycine and beta-branched residues support and modulate peptide helicity in membrane environments.
abstract: Transmembrane (TM) segments of integral membrane proteins are putatively alpha-helical in conformation once inserted into the membrane, yet consist of primary sequences rich in residues known in soluble proteins as helix-breakers (Gly) and beta-sheet promoters (Ile, Val, Thr). To examine the specific 2 degrees structure propensities of such residues in membrane environments, we have designed and synthesized a series of 20-residue peptides with 'guest' hydrophobic segments--expected to provide three turns of incipient alpha-helix content--embedded in 'host' hydrophilic (Lys-Ser) matrices. Circular dichroism (CD) spectra of the model peptides in water showed that significant helical content was observed only for peptides with high Ala content; others behaved as 'random coils'. However, in the membrane-mimetic environment of sodium dodecylsulfate (SDS) micelles, it was found that Gly can be accommodated as readily as Ala, and Ile or Val as readily as Leu, in hydrophobic alpha-helices. Further subtleties of structural preferences could be observed in electrically-neutral lyso-phosphatidylcholine (LPC) micelles, where helical propensity decreased in the order Ala-Leu-rich > Gly-Leu-rich > Gly-Ile(Val)-rich hydrophobic segments. The results conjure a role of environment-dependent helix-modulation for Gly, Ile, and Val residues--and suggest that these residues may provide, in part, the structural basis for conformational transitions within or adjacent to membrane domains, such as those accompanying membrane insertion and/or required for transport or signalling functions.
authors.affiliation: Division of Biochemistry Research, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: S C
authors.initials: SC
authors.lastname: Li
authors.forename: C M
authors.initials: CM
authors.lastname: Deber
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D005998:Glycine; D007532:Isoleucine; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013912:Threonine; D014633:Valine
chemical_list: D010455:Peptides; D011506:Proteins; D007532:Isoleucine; D013912:Threonine; D014633:Valine; D005998:Glycine