Stepinac Emma, Landrein Nicolas, Skwarzyńska Daria, Wójcik Patrycja, Lesigang Johannes, Lučić Iva, He Cynthia Y, Bonhivers Mélanie, Robinson Derrick R, Dong Gang
Max Perutz Labs, Vienna Biocenter, Center for Medical Biochemistry, Medical University of Vienna, 1030 Vienna, Austria.
University of Bordeaux, CNRS, Microbiologie Fondamentale et Pathogénicité, UMR 5234, 33000 Bordeaux, France.
iScience. 2021 Apr 20;24(5):102422. doi: 10.1016/j.isci.2021.102422. eCollection 2021 May 21.
Extended synaptotagmins (E-Syts) localize at membrane contact sites between the endoplasmic reticulum (ER) and the plasma membrane to mediate inter-membrane lipid transfer and control plasma membrane lipid homeostasis. All known E-Syts contain an N-terminal transmembrane (TM) hairpin, a central synaptotagmin-like mitochondrial lipid-binding protein (SMP) domain, and three or five C2 domains at their C termini. Here we report an uncharacterized E-Syt from the protist parasite , namely, TbE-Syt. TbE-Syt contains only two C2 domains (C2A and C2B), making it the shortest E-Syt known by now. We determined a 1.5-Å-resolution crystal structure of TbE-Syt-C2B and revealed that it binds lipids via both Ca- and PI(4,5)P-dependent means. In contrast, TbE-Syt-C2A lacks the Ca-binding site but may still interact with lipids via a basic surface patch. Our studies suggest a mechanism for how TbE-Syt tethers the ER membrane tightly to the plasma membrane to transfer lipids between the two organelles.
扩展突触结合蛋白（E-Syts）定位于内质网（ER）和质膜之间的膜接触位点，以介导膜间脂质转移并控制质膜脂质稳态。所有已知的E-Syts在其N端都含有一个跨膜（TM）发夹结构、一个位于中央的类突触结合线粒体脂质结合蛋白（SMP）结构域，以及在其C端的三个或五个C2结构域。在此，我们报道了一种来自原生生物寄生虫的未被表征的E-Syt，即TbE-Syt。TbE-Syt仅包含两个C2结构域（C2A和C2B），这使其成为目前已知最短的E-Syt。我们确定了TbE-Syt-C2B的分辨率为1.5埃的晶体结构，并揭示它通过依赖于钙和磷脂酰肌醇-4,5-二磷酸（PI(4,5)P）的方式结合脂质。相比之下，TbE-Syt-C2A缺乏钙结合位点，但仍可能通过一个碱性表面区域与脂质相互作用。我们的研究提出了一种关于TbE-Syt如何将内质网膜紧密连接到质膜以在这两个细胞器之间转移脂质的机制。
