Structural studies of the shortest extended synaptotagmin with only two C2 domains from Trypanosoma brucei
Emma Stepinac,
Nicolas Landrein,
Daria Skwarzyńska,
Patrycja Wójcik,
Johannes Lesigang,
Iva Lučić,
Cynthia Y. He,
Mélanie Bonhivers,
Derrick R. Robinson,
Gang Dong
Affiliations
Emma Stepinac
Max Perutz Labs, Vienna Biocenter, Center for Medical Biochemistry, Medical University of Vienna, 1030 Vienna, Austria
Nicolas Landrein
University of Bordeaux, CNRS, Microbiologie Fondamentale et Pathogénicité, UMR 5234, 33000 Bordeaux, France
Daria Skwarzyńska
Max Perutz Labs, Vienna Biocenter, Center for Medical Biochemistry, Medical University of Vienna, 1030 Vienna, Austria; Silesian University of Technology, Gliwice, Poland
Patrycja Wójcik
Max Perutz Labs, Vienna Biocenter, Center for Medical Biochemistry, Medical University of Vienna, 1030 Vienna, Austria; Silesian University of Technology, Gliwice, Poland
Johannes Lesigang
Max Perutz Labs, Vienna Biocenter, Center for Medical Biochemistry, Medical University of Vienna, 1030 Vienna, Austria
Iva Lučić
Max Perutz Labs, Vienna Biocenter, Center for Medical Biochemistry, Medical University of Vienna, 1030 Vienna, Austria
Cynthia Y. He
Department of Biological Sciences, Center for BioImaging Sciences, National University of Singapore, Singapore, Singapore
Mélanie Bonhivers
University of Bordeaux, CNRS, Microbiologie Fondamentale et Pathogénicité, UMR 5234, 33000 Bordeaux, France
Derrick R. Robinson
University of Bordeaux, CNRS, Microbiologie Fondamentale et Pathogénicité, UMR 5234, 33000 Bordeaux, France
Gang Dong
Max Perutz Labs, Vienna Biocenter, Center for Medical Biochemistry, Medical University of Vienna, 1030 Vienna, Austria; Corresponding author
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.
