FEBS Letters | |
Glycine and β‐branched residues support and modulate peptide helicity in membrane environments | |
Deber, Charles M.2  Li, Shun-Cheng1  | |
[1] Division of Biochemistry Research, Research Institute, The Hospital for Sick Children Toronto M5G 1A8, Ontario, Canada;Department of Biochemistry, University of Toronto, Toronto M5S IA8, Ontario, Canada | |
关键词: Peptide; Conformation; Membrane; α-Helix; Circular dichroism; Hydrophobic segment; Fmoc; 9-fluorenylmethoxycarbonyl; HOBt; 1-hydroxybenzotriazole; ODhbt; 3; 4-dihydro-3-hydroxy-4-oxo-1; 2; 3-benzotriazine; TFA; trifluoroacetic acid; SDS; sodium dodecylsulfate; HPLC; high performance liquid chromatography; CD; circular dichroism; TM; transmembrane; LPC; L-α-(myristoyl)-lysophosphatidylcholine; | |
DOI : 10.1016/0014-5793(92)81106-V | |
学科分类:生物化学/生物物理 | |
来源: John Wiley & Sons Ltd. | |
【 摘 要 】
Transmembrane (TM) segments of integral membrane proteins are putatively α-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 β-sheet promoters (Ile, Val, Thr). To examine the specific 2° 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 α-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 α-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.
【 授权许可】
Unknown
【 预 览 】
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