美国俄勒冈健康与科学大学Sarah Clark小组报道了桥状脂质转移蛋白脂质转移的结构基础。相关论文于2025年4月23日发表于国际顶尖学术期刊《自然》杂志上。

研究团队提出了从转基因秀丽隐杆线虫中分离的天然LPD-3 BLTP复合物的亚基组成和低温电镜结构。LPD-3折叠成一个细长的棒状通道，其内部充满有序的脂质分子，这些脂质分子通过通道一侧的可电离残基轨迹进行协调。LPD-3与两种以前未被表征的蛋白质形成复合物，其中一种该研究组命名为Spigot，另一种仍未命名。Spigot与LPD-3的N端相互作用，脂质有望进入通道，多个模型系统的实验表明Spigot在BLTP功能中具有保守作用。他们的LPD-3复合物结构数据揭示了蛋白质-脂质相互作用，为天然LPD-3复合物如何介导大量脂质转运提供了一个模型，并为BLTP的机制研究提供了基础。

据介绍，桥状脂质转运蛋白（BLTPs）是一种进化上保守的蛋白家族，定位于膜接触部位，被认为介导脂质从供体膜（通常是内质网）向受体膜（如细胞或细胞器）的大量转移。尽管BLTPs对多种细胞功能至关重要，但对其结构、组成和脂质转移机制的研究仍然很少。

附：英文原文

Title: Structural basis of lipid transfer by a bridge-like lipid-transfer protein

Author: Kang, Yunsik, Lehmann, Katherine S., Long, Hannah, Jefferson, Amanda, Purice, Maria, Freeman, Marc, Clark, Sarah

Issue&Volume: 2025-04-23

Abstract: Bridge-like lipid-transport proteins (BLTPs) are an evolutionarily conserved family of proteins that localize to membrane-contact sites and are thought to mediate the bulk transfer of lipids from a donor membrane, typically the endoplasmic reticulum, to an acceptor membrane, such as that of the cell or an organelle1. Although BLTPs are fundamentally important for a wide array of cellular functions, their architecture, composition and lipid-transfer mechanisms remain poorly characterized. Here we present the subunit composition and the cryogenic electron microscopy structure of the native LPD-3 BLTP complex isolated from transgenic Caenorhabditis elegans. LPD-3 folds into an elongated, rod-shaped tunnel of which the interior is filled with ordered lipid molecules that are coordinated by a track of ionizable residues that line one side of the tunnel. LPD-3 forms a complex with two previously uncharacterized proteins, one of which we have named Spigot and the other of which remains unnamed. Spigot interacts with the N-terminal end of LPD-3 where lipids are expected to enter the tunnel, and experiments in multiple model systems indicate that Spigot has a conserved role in BLTP function. Our LPD-3 complex structural data reveal protein–lipid interactions that suggest a model for how the native LPD-3 complex mediates bulk lipid transport and provides a foundation for mechanistic studies of BLTPs.

DOI: 10.1038/s41586-025-08918-y

Source: https://www.nature.com/articles/s41586-025-08918-y