Structural studies of the shortest extended synaptotagmin with only two C2 domains from Trypanosoma brucei

• Main Authors: Emma Stepinac, Nicolas Landrein, Daria Skwarzyńska, Patrycja Wójcik, Johannes Lesigang, Iva Lučić, Cynthia Y. He, Mélanie Bonhivers, Derrick R. Robinson, Gang Dong
• Format: Article
• Language: English
• Published: Elsevier 2021-05-01
• Series: iScience
• Subjects: Biochemistry; Medical Biochemistry; Biochemistry Applications
• Online Access: http://www.sciencedirect.com/science/article/pii/S2589004221003904
• ISSN: 2589-0042

Summary: 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 Trypanosoma brucei, 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 Ca2+- and PI(4,5)P2-dependent means. In contrast, TbE-Syt-C2A lacks the Ca2+-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.