包含色氨酸残基的两亲性α-螺旋肽的离子通道稳定化的系统设计和验证,ACS Omega

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包含色氨酸残基的两亲性α-螺旋肽的离子通道稳定化的系统设计和验证
ACS Omega ( IF 3.7 ) Pub Date : 2020-12-29 , DOI: 10.1021/acsomega.0c05254
Keita Shigedomi ₁ , Satoshi Osada ₁ , Masoud Jelokhani-Niaraki ₂ , Hiroaki Kodama ₁

Affiliation

芳香族相互作用（例如π-π相互作用和阳离子-π相互作用）存在于膜蛋白中，并在结构和功能中均起重要作用。为了系统地研究芳香族残基对肽形成的离子通道的结构稳定性和离子渗透性的影响，我们设计了几种在两亲性α-螺旋肽中的不同位置带有一个或两个色氨酸（Trp）残基的肽。圆二色性（CD）研究表明，Trp残基在这些设计的肽中具有更好的自缔合性。系统设计的在每个螺旋末端带有两个Trp的二取代肽证明了聚集引起的分子间Trp-Trp相互作用。在脂质体存在下，肽亲水面上的Trp增强了与脂质膜的相互作用，从而增加了两亲性α-螺旋含量。适当掺入和定位Trp可使肽形成更稳定的通道，并与Trp二取代肽产生显着影响。一系列此类肽的离子通道形成能力表明，相邻跨膜螺旋中Trp和Lys残基之间的阳离子-π相互作用有助于显着稳定通道结构。

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Systematic Design and Validation of Ion Channel Stabilization of Amphipathic α-Helical Peptides Incorporating Tryptophan Residues

Aromatic interactions such as π–π interaction and cation−π interaction are present in membrane proteins and play important roles in both structure and function. To systematically investigate the effect of aromatic residues on the structural stability and ion permeability of peptide-formed ion channels, we designed several peptides with one or two tryptophan (Trp) residues incorporated at different positions in amphipathic α-helical peptides. Circular dichroism (CD) studies revealed the preferable position of Trp residues for self-association in these designed peptides. Systematically designed di-substituted peptides with two Trps at each helix termini demonstrated intermolecular Trp–Trp interactions caused by aggregation. In the presence of liposomes, Trp on the hydrophilic face of the peptide enhanced interaction with the lipid membrane to increase the amphipathic α-helical contents. Appropriate incorporation and positioning of Trp enabled peptides to form more stable channels and had notable effects with Trp di-substituted peptides. The ion channel forming capability of a series of these peptides showed that the cation−π interactions between Trp and Lys residues in adjacent transmembrane helices contribute to remarkable stabilization of the channel structure.

更新日期：2021-01-12

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