SPFH-domain proteins are found in almost all organisms across three domains: archaea, bacteria, and eukaryotes. In eukaryotic organelles, their subfamilies exhibit overlapping distribution and functions; thus, the rationality of annotation to discriminate these subfamilies remains unclear. In this review, the binding ability of prokaryotic SPFH-domain proteins towards nonpolar polyisoprenoides such as squalene and lycopene, rather than cholesterol, is discussed. The hydrophobic region at the C-terminus of SPFH-domain proteins constitutes the main region that binds apolar polyisoprenoid lipids as well as cholesterol and substantively contributes towards lipid raft formation as these regions are self-assembled together with specific lipids. Because the scaffolding proteins caveolins show common topological properties with SPFH-domain proteins such as stomatin and flotillin, the α-helical segments of stomatin proteins can flexibly move along with the membrane surface, with such movement potentially leading to membrane bending via lipid raft clustering through the formation of high order homo-oligomeric complexes of SPFH-domain proteins. We also discuss the functional significance and ancient origin of SPFH-domain proteins and the NfeD protein (STOPP) operon, which can be traced back to the ancient living cells that diverged and evolved to archaea and bacteria. Based on the molecular mechanism whereby the STOPP-protease degrades the C-terminal hydrophobic clusters of SPFH-domain proteins, it is conceivable that STOPP-protease might control the physicochemical properties of lipid rafts.

中文翻译：

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脂质筏标志物stomatin，probidin，flotilin和HflK / C（SPFH）域蛋白与NfeD蛋白形成操纵子，并与非极性聚异戊二烯脂一起起作用。

SPFH结构域蛋白几乎遍布以下三个结构域的所有生物中：古细菌，细菌和真核生物。在真核细胞器中，它们的亚科表现出重叠的分布和功能。因此，用注解来区分这些亚科的合理性仍然不清楚。在这篇综述中，讨论了原核SPFH结构域蛋白与非极性聚异戊二烯如角鲨烯和番茄红素而不是胆固醇的结合能力。SPFH结构域蛋白C端的疏水区构成了结合非极性聚异戊二烯脂以及胆固醇的主要区域，并且由于这些区域与特定脂质一起自组装，因此在很大程度上形成了脂筏。由于脚手架蛋白小窝蛋白与SPFH域蛋白（例如，stomatin和flotillin）具有共同的拓扑特性，因此，stomatin蛋白的α-螺旋片段可以随膜表面灵活移动，这种移动可能会导致脂质筏聚集，从而导致膜弯曲。 SPFH域蛋白的高阶同聚寡聚体的形成。我们还讨论了SPFH域蛋白和NfeD蛋白（STOPP）操纵子的功能意义和远古起源，其起源可以追溯到古老的活细胞，该细胞分化并演变为古细菌和细菌。基于STOPP蛋白酶降解SPFH域蛋白的C端疏水簇的分子机制，可以想象STOPP蛋白酶可以控制脂质筏的理化性质。