Structural insights into cardiolipin replacement by phosphatidylglycerol in a cardiolipin-lacking yeast respiratory supercomplex.
Structural insights into cardiolipin replacement by phosphatidylglycerol in a cardiolipin-lacking yeast respiratory supercomplex.
复制标题
DOI：
10.1038/s41467-023-38441-5
复制
发表时间：
2023-05-15
影响因子：
16.6
通讯作者：
Dowhan, William
中科院分区：
文献类型：
--
作者：
Hryc, Corey F.;Mallampalli, Venkata K. P. S.;Bovshik, Evgeniy I.;Azinas, Stavros;Fan, Guizhen;Serysheva, Irina I.;Sparagna, Genevieve C.;Baker, Matthew L.;Mileykovskaya, Eugenia;Dowhan, William
心磷脂是线粒体膜的标志性磷脂。尽管心磷脂在支持呼吸超复合体组织中具有重要意义，但对这种脂质-蛋白质相互作用的机制仍缺乏了解。为了解决心磷脂在超复合物组织中的重要作用，我们报告了一个野生型超复合物（IV 1 III 2 IV 1）和一个超复合物（III 2 IV 1）的冷冻电镜结构，从缺乏心磷脂的酿酒酵母突变体中分离出来，分别在3.2和3.3分辨率，并证明了在III 2 IV 1中的磷脂酰甘油占据了与心磷脂在IV 1 III 2 IV 1中相似的位置。这些复合物内的脂质-蛋白质相互作用不同，这可以想象是突变线粒体中IV 1 III 2 IV 1水平降低和III 2 IV 1水平升高以及游离III 2和IV水平升高的基础。在这里，我们表明，阴离子磷脂与正氨基酸相互作用，并出现成核的磷脂结构域在各个复合物之间的界面，这抑制电荷排斥和进一步稳定的相互作用，分别在各个复合物之间。阴离子磷脂是否需要呼吸超复合物（SC）的形成尚不清楚。在这里，作者以3.2- 3.3 μ m的分辨率解析了来自野生型和心磷脂缺陷型酵母菌株的SC，以表明心磷脂可以被磷脂酰甘油取代。
Cardiolipin is a hallmark phospholipid of mitochondrial membranes. Despite established significance of cardiolipin in supporting respiratory supercomplex organization, a mechanistic understanding of this lipid-protein interaction is still lacking. To address the essential role of cardiolipin in supercomplex organization, we report cryo-EM structures of a wild type supercomplex (IV1III2IV1) and a supercomplex (III2IV1) isolated from a cardiolipin-lacking Saccharomyces cerevisiae mutant at 3.2-Å and 3.3-Å resolution, respectively, and demonstrate that phosphatidylglycerol in III2IV1 occupies similar positions as cardiolipin in IV1III2IV1. Lipid-protein interactions within these complexes differ, which conceivably underlies the reduced level of IV1III2IV1 and high levels of III2IV1 and free III2 and IV in mutant mitochondria. Here we show that anionic phospholipids interact with positive amino acids and appear to nucleate a phospholipid domain at the interface between the individual complexes, which dampen charge repulsion and further stabilize interaction, respectively, between individual complexes. Whether anionic phospholipids required for respiratory supercomplex (SC) formation is unclear. Here authors resolve SCs from a wild type and cardiolipin-deficient yeast strain at 3.2- 3.3 Å resolution to show that cardiolipin can be replaced by phosphatidylglycerol.
登录
查看更多内容
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
7.4
作者：
Huang, Zhentai;Jiang, Jianfei;Kagan, Valerian E.
通讯作者：
Kagan, Valerian E.
影响因子：
4.8
作者：
Bazan, Soledad;Mileykovskaya, Eugenia;Dowhan, William
通讯作者：
Dowhan, William
DOI：
10.1107/s0907444909042073
发表时间：
2010-01
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Chen VB;Arendall WB 3rd;Headd JJ;Keedy DA;Immormino RM;Kapral GJ;Murray LW;Richardson JS;Richardson DC
通讯作者：
Richardson DC
影响因子：
62.1
作者：
Brzezinski P;Moe A;Ädelroth P
通讯作者：
Ädelroth P