Brasseur R, Vanloo B, Deleys R, Lins L, Labeur C, Taveirne J, Ruysschaert J M, Rosseneu M
Free University of Brussels, Belgium.
Biochim Biophys Acta. 1993 Sep 29;1170(1):1-7. doi: 10.1016/0005-2760(93)90168-9.
Amphipathic helical peptides are the lipid-binding motives of the plasma apolipoproteins, and synthetic peptide analogs have been used to unravel the mechanism of lipid association within this class of proteins. Hydrophobic interactions between the apolar amino acid residues belonging to the hydrophobic face of the amphipathic helices and the lipids are the major driving forces in the peptide-lipid association to form discoidal complexes. Ionic interactions and salt bridge formation between contiguous peptide chains in the complex can, however, contribute to the overall stability of the lipid-protein particle. This was studied by designing peptide analogs to the helical repeats of the apolipoproteins with variable degrees of salt bridge formation between adjacent peptide chains. The most stable conformation for pairs of synthetic peptides was calculated by energy minimisation together with the energy of interaction between peptides. The sequence of the peptides was derived from that of the 18A peptide synthesized by Segrest et al., and the theoretical calculations confirmed that ionic interactions between residues close to each other, along the edge of two adjacent anti-parallel peptides, can significantly contribute towards the stability of a peptide-phospholipid complex.
两亲性螺旋肽是血浆载脂蛋白的脂质结合基序，合成肽类似物已被用于揭示这类蛋白质中脂质缔合的机制。属于两亲性螺旋疏水表面的非极性氨基酸残基与脂质之间的疏水相互作用是肽 - 脂质缔合形成盘状复合物的主要驱动力。然而，复合物中相邻肽链之间的离子相互作用和盐桥形成有助于脂质 - 蛋白质颗粒的整体稳定性。通过设计与载脂蛋白螺旋重复序列类似的肽类似物来研究这一点，这些肽类似物在相邻肽链之间具有不同程度的盐桥形成。通过能量最小化以及肽之间的相互作用能来计算合成肽对的最稳定构象。肽的序列源自Segrest等人合成的18A肽的序列，理论计算证实，沿着两条相邻反平行肽边缘彼此靠近的残基之间的离子相互作用可显著有助于肽 - 磷脂复合物的稳定性。
