Lins L, Brasseur R
Centre de Biophysique Moléculaire Numérique, FSAGx, Belgium.
J Pept Sci. 2008 Apr;14(4):416-22. doi: 10.1002/psc.971.
Tilted peptides are short hydrophobic protein fragments characterized by an asymmetric distribution of their hydrophobic residues when helical. They are able to interact with a hydrophobic/hydrophilic interface (such as a lipid membrane) and to destabilize the organized system into which they insert. They were detected in viral fusion proteins and in proteins involved in different biological processes involving membrane insertion or translocation of the protein in which they are found. In this paper, we have analysed different protein domains related to membrane insertion with regard to their tilted properties. They are the N-terminal signal peptide of the filamentous haemagglutinin (FHA), a Bordetella pertussis protein secreted in high amount and the hydrophobic domain from proteins forming pores (i.e. ColIa, Bax and Bcl-2). From the predictions and the experimental approaches, we suggest that tilted peptides found in those proteins could have a more general role in the mechanism of insertion/translocation of proteins into/across membranes. For the signal sequences, they could help the protein machinery involved in protein secretion to be more active. In the case of toroidal pore formation, they could disturb the lipids, facilitating the insertion of the other more hydrophilic helices.
倾斜肽是短的疏水蛋白片段，其特征在于螺旋时疏水残基的不对称分布。它们能够与疏水/亲水界面（如脂质膜）相互作用，并使它们插入的有序系统不稳定。它们在病毒融合蛋白以及参与不同生物过程（包括膜插入或它们所在蛋白质的易位）的蛋白质中被检测到。在本文中，我们分析了与膜插入相关的不同蛋白质结构域的倾斜特性。它们是丝状血凝素（FHA）的N端信号肽，FHA是一种大量分泌的百日咳博德特氏菌蛋白，以及形成孔的蛋白质（即ColIa, Bax和Bcl-2）的疏水结构域。从预测和实验方法来看，我们认为在这些蛋白质中发现的倾斜肽在蛋白质插入/跨膜易位机制中可能具有更普遍的作用。对于信号序列，它们可以帮助参与蛋白质分泌的蛋白质机器更活跃。在形成环形孔的情况下，它们可以干扰脂质，促进其他更亲水螺旋的插入。
