Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY, 11794, USA.
Laboratoire de Physique de l'École normale supérieure, ENS, Université PSL, CNRS, Sorbonne Université, Université Paris Cité, F-75005, Paris, France.
Nat Commun. 2023 Jun 2;14(1):3204. doi: 10.1038/s41467-023-38725-w.
Lipid droplets (LDs) are dynamic organelles that contain an oil core mainly composed of triglycerides (TAG) that is surrounded by a phospholipid monolayer and LD-associated proteins called perilipins (PLINs). During LD biogenesis, perilipin 3 (PLIN3) is recruited to nascent LDs as they emerge from the endoplasmic reticulum. Here, we analyze how lipid composition affects PLIN3 recruitment to membrane bilayers and LDs, and the structural changes that occur upon membrane binding. We find that the TAG precursors phosphatidic acid and diacylglycerol (DAG) recruit PLIN3 to membrane bilayers and define an expanded Perilipin-ADRP-Tip47 (PAT) domain that preferentially binds DAG-enriched membranes. Membrane binding induces a disorder to order transition of alpha helices within the PAT domain and 11-mer repeats, with intramolecular distance measurements consistent with the expanded PAT domain adopting a folded but dynamic structure upon membrane binding. In cells, PLIN3 is recruited to DAG-enriched ER membranes, and this requires both the PAT domain and 11-mer repeats. This provides molecular details of PLIN3 recruitment to nascent LDs and identifies a function of the PAT domain of PLIN3 in DAG binding.
脂滴（LDs）是一种动态细胞器，内部含有以甘油三酯（TAG）为主的油核，周围是一层磷脂单层和称为脂滴相关蛋白（PLINs）的 LD 相关蛋白。在 LD 生物发生过程中，当新形成的 LD 从内质网中出现时， perilipin 3（PLIN3）被招募到初生 LD 上。在这里，我们分析了脂质组成如何影响 PLIN3 向膜双层和 LD 的募集，以及在膜结合时发生的结构变化。我们发现 TAG 前体磷脂酸和二酰基甘油（DAG）将 PLIN3 招募到膜双层，并定义了一个扩展的 Perilipin-ADRP-Tip47（PAT）结构域，该结构域优先结合富含 DAG 的膜。膜结合诱导 PAT 结构域和 11 -mer 重复内的α螺旋从无序到有序的转变，分子内距离测量结果与扩展的 PAT 结构域在膜结合时采用折叠但动态的结构一致。在细胞中，PLIN3 被招募到富含 DAG 的内质网膜上，这既需要 PAT 结构域，也需要 11 -mer 重复。这为 PLIN3 向新生 LD 的募集提供了分子细节，并确定了 PLIN3 的 PAT 结构域在 DAG 结合中的功能。
