Department of Medicinal Chemistry, College of Pharmacy, Ann Arbor, MI 48109-1065, United States.
Biochim Biophys Acta Biomembr. 2018 Feb;1860(2):364-377. doi: 10.1016/j.bbamem.2017.11.002. Epub 2017 Nov 10.
A comparative analysis of 6039 single-pass (bitopic) membrane proteins from six evolutionarily distant organisms was performed based on data from the Membranome database. The observed repertoire of bitopic proteins is significantly enlarged in eukaryotic cells and especially in multicellular organisms due to the diversification of enzymes, emergence of proteins involved in vesicular trafficking, and expansion of receptors, structural, and adhesion proteins. The majority of bitopic proteins in multicellular organisms are located in the plasma membrane (PM) and involved in cell communication. Bitopic proteins from different membranes significantly diverge in terms of their biological functions, size, topology, domain architecture, physical properties of transmembrane (TM) helices and propensity to form homodimers. Most proteins from eukaryotic PM and endoplasmic reticulum (ER) have the N-out topology. The predicted lengths of TM helices and hydrophobic thicknesses, stabilities and hydrophobicities of TM α-helices are the highest for proteins from eukaryotic PM, intermediate for proteins from prokaryotic cells, ER and Golgi apparatus, and lowest for proteins from mitochondria, chloroplasts, and peroxisomes. Tyr and Phe residues accumulate at the cytoplasmic leaflet of PM and at the outer leaflet of membranes of bacteria, Golgi apparatus, and nucleus. The propensity for dimerization increases from unicellular to multicellular eukaryotes, from enzymes to receptors, and from intracellular membrane proteins to PM proteins. More than half of PM proteins form homodimers with a 2:1 ratio of right-handed to left-handed helix packing arrangements. The inverse ratio (1:2) was observed for dimers from the ER, Golgi and vesicles.
基于 Membranome 数据库的数据，对来自六个进化上相距较远的生物体的 6039 个单通道（双位）膜蛋白进行了比较分析。真核细胞中二价蛋白的明显增多，尤其是在多细胞生物中，这是由于酶的多样化、参与囊泡运输的蛋白质的出现以及受体、结构和黏附蛋白的扩张。大多数多细胞生物中的双价蛋白位于质膜（PM）中，并参与细胞通讯。不同膜的双价蛋白在其生物学功能、大小、拓扑结构、结构域架构、跨膜（TM）螺旋的物理性质和形成同源二聚体的倾向方面存在显著差异。大多数来自真核 PM 和内质网（ER）的蛋白质具有 N 端在外的拓扑结构。TM 螺旋的预测长度、TM α-螺旋的疏水性厚度、稳定性和疏水性，对于来自真核 PM 的蛋白质最高，对于来自原核细胞、ER 和高尔基体的蛋白质中等，对于来自线粒体、叶绿体和过氧化物酶体的蛋白质最低。Tyr 和 Phe 残基在 PM 的细胞质小叶和细菌、高尔基体和核的膜外小叶中积累。从单细胞真核生物到多细胞真核生物，从酶到受体，以及从细胞内膜蛋白到 PM 蛋白，二聚体的倾向增加。超过一半的 PM 蛋白以右手和左手螺旋包装排列 2:1 的比例形成同源二聚体。ER、高尔基体和囊泡中的二聚体观察到相反的比例（1:2）。
