Departament de Bioquímica i Biologia Molecular, Universitat de València, Burjassot, Spain.
PLoS One. 2012;7(9):e44263. doi: 10.1371/journal.pone.0044263. Epub 2012 Sep 12.
The vast majority of membrane proteins are anchored to biological membranes through hydrophobic α-helices. Sequence analysis of high-resolution membrane protein structures show that ionizable amino acid residues are present in transmembrane (TM) helices, often with a functional and/or structural role. Here, using as scaffold the hydrophobic TM domain of the model membrane protein glycophorin A (GpA), we address the consequences of replacing specific residues by ionizable amino acids on TM helix insertion and packing, both in detergent micelles and in biological membranes. Our findings demonstrate that ionizable residues are stably inserted in hydrophobic environments, and tolerated in the dimerization process when oriented toward the lipid face, emphasizing the complexity of protein-lipid interactions in biological membranes.
绝大多数膜蛋白通过疏水α-螺旋锚定在生物膜上。高分辨率膜蛋白结构的序列分析表明，可离子化的氨基酸残基存在于跨膜（TM）螺旋中，这些残基通常具有功能和/或结构作用。在这里，我们使用模型膜蛋白糖蛋白 A（GpA）的疏水 TM 结构域作为支架，研究了在去污剂胶束和生物膜中，用可离子化氨基酸取代特定残基对 TM 螺旋插入和堆积的影响。我们的研究结果表明，可离子化残基能够稳定地插入疏水环境中，并且在朝向脂质面的方向上，在二聚化过程中也能被容忍，这强调了生物膜中蛋白质-脂质相互作用的复杂性。
