Division of Pharmaceutical Sciences, University of Wisconsin-Madison, Madison, WI 53705-2222, USA.
UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London, EC1V 9EL, UK.
Trends Cell Biol. 2022 Nov;32(11):962-974. doi: 10.1016/j.tcb.2022.03.011. Epub 2022 Apr 28.
Lipid transfer proteins mediate nonvesicular transport of lipids at membrane contact sites to regulate the lipid composition of organelle membranes. Recently, a new type of bridge-like lipid transfer protein has emerged; these proteins contain a long hydrophobic groove and can mediate bulk transport of lipids between organelles. Here, we review recent insights into the structure of these proteins and identify a repeating modular unit that we propose to name the repeating β-groove (RBG) domain. This new structural understanding conceptually unifies all the RBG domain-containing lipid transfer proteins as members of an RBG protein superfamily. We also examine the biological functions of these lipid transporters in normal physiology and disease and speculate on the evolutionary origins of RBG proteins in bacteria.
脂质转运蛋白在膜接触位点介导非囊泡脂质转运,以调节细胞器膜的脂质组成。最近,出现了一种新型桥接脂质转运蛋白;这些蛋白质含有长疏水性槽,可介导细胞器之间的脂质批量转运。在这里,我们回顾了这些蛋白质结构的最新见解,并确定了一个重复的模块化单元,我们提议将其命名为重复β槽(RBG)结构域。这种新的结构理解将所有含有 RBG 结构域的脂质转运蛋白概念上统一为 RBG 蛋白超家族的成员。我们还研究了这些脂质转运蛋白在正常生理和疾病中的生物学功能,并推测了 RBG 蛋白在细菌中的进化起源。