Mechanism of lipid droplet formation by the yeast Sei1/Ldb16 Seipin complex.
Mechanism of lipid droplet formation by the yeast Sei1/Ldb16 Seipin complex.
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DOI：
10.1038/s41467-021-26162-6
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发表时间：
2021-10-08
影响因子：
16.6
通讯作者：
Carvalho P
中科院分区：
文献类型：
--
作者：
Klug YA;Deme JC;Corey RA;Renne MF;Stansfeld PJ;Lea SM;Carvalho P
脂滴（ld）是一种通用的脂质储存细胞器，其核心是中性脂质，如三酰基甘油，被磷脂单层包围。这种独特的结构是在LD生物发生过程中在内质网（ER）位点产生的，内质网是由Seipin标记的，Seipin是一种在脂肪营养不良中发生突变的保守膜蛋白。本文采用结构、生化和分子动力学模拟方法揭示了酵母Seipin Sei1及其膜伴侣Ldb16形成LD的机制。我们发现，Sei1管腔结构域组装了一个同质寡聚环，与其他seipin相比，它不能浓缩三酰基甘油。相反，Sei1定位Ldb16，通过关键羟基残基将三酰基甘油浓缩在Sei1环内。Sei1跨膜片段进一步促进了三酰甘油向复合物的募集，这也控制了Ldb16的稳定性。因此，我们提出Sei1/Ldb16复合物和其他Seipins的LD组装需要通过内质网膜和管腔中的不同元件进行连续的三酰基甘油浓缩步骤。脂滴的形成是由保守的膜蛋白Seipin通过一种未知的机制调控的。本文采用结构、生化和分子动力学模拟等方法，揭示酵母Seipin Sei1及其伙伴Ldb16形成脂滴的机制。
Lipid droplets (LDs) are universal lipid storage organelles with a core of neutral lipids, such as triacylglycerols, surrounded by a phospholipid monolayer. This unique architecture is generated during LD biogenesis at endoplasmic reticulum (ER) sites marked by Seipin, a conserved membrane protein mutated in lipodystrophy. Here structural, biochemical and molecular dynamics simulation approaches reveal the mechanism of LD formation by the yeast Seipin Sei1 and its membrane partner Ldb16. We show that Sei1 luminal domain assembles a homooligomeric ring, which, in contrast to other Seipins, is unable to concentrate triacylglycerol. Instead, Sei1 positions Ldb16, which concentrates triacylglycerol within the Sei1 ring through critical hydroxyl residues. Triacylglycerol recruitment to the complex is further promoted by Sei1 transmembrane segments, which also control Ldb16 stability. Thus, we propose that LD assembly by the Sei1/Ldb16 complex, and likely other Seipins, requires sequential triacylglycerol-concentrating steps via distinct elements in the ER membrane and lumen. Lipid droplet biogenesis is orchestrated by the conserved membrane protein Seipin via an unknown mechanism. Here, the authors use structural, biochemical and molecular dynamics simulation approaches to reveal the mechanism of lipid droplet formation by the yeast Seipin Sei1 and its partner Ldb16.
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影响因子：
6.5
作者：
Currie E;Guo X;Christiano R;Chitraju C;Kory N;Harrison K;Haas J;Walther TC;Farese RV Jr
通讯作者：
Farese RV Jr
影响因子：
3.4
作者：
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通讯作者：
Thiam, Abdou Rachid
DOI：
10.1083/jcb.201505067
发表时间：
2015-10-26
期刊：
The Journal of cell biology
影响因子：
--
作者：
Choudhary V;Ojha N;Golden A;Prinz WA
通讯作者：
Prinz WA
影响因子：
7.8
作者：
Choudhary, Vineet;El Atab, Ola;Schneiter, Roger
通讯作者：
Schneiter, Roger
DOI：
10.1083/jcb.201502070
发表时间：
2015-11-23
期刊：
The Journal of cell biology
影响因子：
--
作者：
Grippa A;Buxó L;Mora G;Funaya C;Idrissi FZ;Mancuso F;Gomez R;Muntanyà J;Sabidó E;Carvalho P
通讯作者：
Carvalho P