Nature:新的一類磷脂醯絲氨酸運輸蛋白

真核細胞被一系列具有獨特類脂組成的、在功能上專門化的、與膜結合在一起的細胞器在內部分成不同部分。在這項研究中，Anne-Claude Gavin及同事確定了芽殖酵母中所有類脂轉移蛋白的類脂結合特徵，發現了一個亞類的以前沒有被識別出的「氧甾酮結合蛋白」(OSBPs)，後者在磷脂醯絲氨酸的自穩中發揮功能，運輸而不是轉移固醇。系統發生分析顯示，類似的OSPBs具有廣泛保守性，包括在人體中——在人體中它們與包括癌症和代謝綜合症在內的病理相關。（生物谷 Bioon.com）

生物谷推薦的英文摘要

Nature doi:10.1038/nature12430

Interactome map uncovers phosphatidylserine transport by oxysterol-binding proteins

Kenji Maeda,  Kanchan Anand,  Antonella Chiapparino,  Arun Kumar,  Mattia Poletto,  Marko Kaksonen  & Anne-Claude Gavin

The internal organization of eukaryotic cells into functionally specialized, membrane-delimited organelles of unique composition implies a need for active, regulated lipid transport. Phosphatidylserine (PS), for example, is synthesized in the endoplasmic reticulum and then preferentially associates—through mechanisms not fully elucidated—with the inner leaflet of the plasma membrane1, 2, 3. Lipids can travel via transport vesicles. Alternatively, several protein families known as lipid-transfer proteins (LTPs) can extract a variety of specific lipids from biological membranes and transport them, within a hydrophobic pocket, through aqueous phases4, 5, 6, 7. Here we report the development of an integrated approach that combines protein fractionation and lipidomics to characterize the LTP–lipid complexes formed in vivo. We applied the procedure to 13 LTPs in the yeast Saccharomyces cerevisiae: the six Sec14 homology (Sfh) proteins and the seven oxysterol-binding homology (Osh) proteins. We found that Osh6 and Osh7 have an unexpected specificity for PS. In vivo, they participate in PS homeostasis and the transport of this lipid to the plasma membrane. The structure of Osh6 bound to PS reveals unique features that are conserved among other metazoan oxysterol-binding proteins (OSBPs) and are required for PS recognition. Our findings represent the first direct evidence, to our knowledge, for the non-vesicular transfer of PS from its site of biosynthesis (the endoplasmic reticulum) to its site of biological activity (the plasma membrane). We describe a new subfamily of OSBPs, including human ORP5 and ORP10, that transfer PS and propose new mechanisms of action for a protein family that is involved in several human pathologies such as cancer, dyslipidaemia and metabolic syndrome.