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

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 syna...

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Published in:iScience 2021-05, Vol.24 (5), p.102422, Article 102422
Main Authors: Stepinac, Emma, Landrein, Nicolas, Skwarzyńska, Daria, Wójcik, Patrycja, Lesigang, Johannes, Lučić, Iva, He, Cynthia Y., Bonhivers, Mélanie, Robinson, Derrick R., Dong, Gang
Format: Article
Language:English
Subjects:
Biochemistry
Biochemistry Applications
Biochemistry, Molecular Biology
Biophysics
Cell Behavior
Cellular Biology
Life Sciences
Medical Biochemistry
Microbiology and Parasitology
Molecular biology
Parasitology
Protistology
Subcellular Processes
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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. [Display omitted] •We identified a new type of extended synaptotagmin (E-Syt) in Trypanosoma brucei•TbE-Syt is the shortest known E-Syt with only two C2 domains, C2A and C2B•TbE-Syt-C2B binds lipids via both Ca2+- and PI(4,5)P2-dependent means•Unlike all other known E-Syts, TbE-Syt-C2A and C2B are connected by a flexible loop Biochemistry; Medical Biochemistry; Biochemistry Applications
ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2021.102422