日内瓦大学Anne-Claude Gavin团队取得一项新突破。他们研究出脂质转移蛋白对脂质动员的系统分析。该研究于2026年1月7日发表于国际一流学术期刊《自然》杂志上。

该研究组结合了生化、脂质组学和计算方法系统地表征了LTP-脂质复合物，并测量了LTP功能增益如何影响细胞脂质组。小组在分析的100个LTP中发现了大约一半的结合脂质，确认了已知的配体，同时在大多数LTP家族中发现了新的配体。LTP功能的增加影响了已知和新发现的脂质配体的细胞丰度，表明两种配体的功能相关性相当。利用结构生物信息学，研究小组已经描述了促进脂质选择性的机制，确定了基于头基或酰基链的偏好。小组展示了LTP如何动员其配体的一些基本原理。它们通常与几种脂类相互作用，并表现出广泛的选择性偏好，不仅对特定的头基团，而且对含有一个或两个不饱和物的较短酰基链的脂类也有选择性偏好，这表明只有脂类的亚群被有效动员。这些数据集代表了对不同细胞类型和状态的进一步分析的阻力，例如与病理相关的细胞。

据介绍，脂质转移蛋白（LTPs）维持细胞器膜的特殊脂质组成。在人类中，许多LTPs与疾病有关，但对于大多数人来说，促进转移的货物和辅助脂质仍然未知。

附：英文原文

Title: Systematic analyses of lipid mobilization by human lipid transfer proteins

Author: Titeca, Kevin, Chiapparino, Antonella, Hennrich, Marco L., Trei, Dnes, Moqadam, Mahmoud, Talandashti, Reza, Cuveillier, Camille, van Ek, Larissa, Zukowska, Joanna, Triana, Sergio, Echelard, Florian, Nielsen, Inger dum, Foged, Mads Mller, Gehin, Charlotte, Olechnovic, Kliment, Grudinin, Sergei, Saez-Rodriguez, Julio, Alexandrov, Theodore, Maeda, Kenji, Reuter, Nathalie, Gavin, Anne-Claude

Issue&Volume: 2026-01-07

Abstract: Lipid transfer proteins (LTPs) maintain the specialized lipid compositions of organellar membranes1,2. In humans, many LTPs are implicated in diseases3, but for the majority, the cargo and auxiliary lipids facilitating transfer remain unknown. We have combined biochemical, lipidomic and computational methods to systematically characterize LTP-lipid complexes4 and measure how LTP gains of function affect cellular lipidomes. We identified bound lipids for approximately half of the hundred LTPs analyzed, confirming known ligands, while discovering new ones across most LTP families. Gains in LTP function affected the cellular abundance of both their known and newly identified lipid ligands, indicating comparable functional relevance of the two ligand sets. Using structural bioinformatics, we have characterized mechanisms contributing to lipid selectivity, identifying preferences based on head group or acyl chain. We demonstrate some basic principles of how LTPs mobilise their ligands. They commonly interact with several classes of lipids and exhibit broad but selective preference, not only for particular head groups, but also for lipid species with shorter acyl chains containing one or two unsaturations, suggesting that only subsets of lipid species are efficiently mobilized. The datasets represent a resource for further analysis in different cell types and states, such as those associated with pathologies.

DOI: 10.1038/s41586-025-10040-y

Source: https://www.nature.com/articles/s41586-025-10040-y