Glycine and β‐branched residues support and modulate peptide helicity in membrane environments

FEBS Letters

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