9HHE
Structure of the Ist2 TMEM16 homology domain in the detergent GDN
Summary for 9HHE
| Entry DOI | 10.2210/pdb9hhe/pdb |
| Related | 9HDH 9HDK |
| EMDB information | 52170 |
| Descriptor | Increased sodium tolerance protein 2 (1 entity in total) |
| Functional Keywords | tmem16 proteins, lipid scramblase, lipid transport, membrane contact sites, tethering protein, membrane protein |
| Biological source | Saccharomyces cerevisiae (brewer's yeast) |
| Total number of polymer chains | 2 |
| Total formula weight | 175554.75 |
| Authors | Arndt, M.,Dutzler, R. (deposition date: 2024-11-21, release date: 2025-09-03, Last modification date: 2025-11-26) |
| Primary citation | Arndt, M.,Schweri, A.,Dutzler, R. Structural basis for lipid transport at membrane contact sites by the IST2-OSH6 complex. Nat.Struct.Mol.Biol., 32:2219-2230, 2025 Cited by PubMed Abstract: Membrane contact sites are hubs for interorganellar lipid transport within eukaryotic cells. As a principal tether bridging the endoplasmic reticulum (ER) and the plasma membrane in Saccharomyces cerevisiae, the protein IST2 has a major role during lipid transport between both compartments. Here, we show a comprehensive investigation elucidating the structural and mechanistic properties of IST2 and its interaction with the soluble lipid transfer protein OSH6. The ER-embedded transmembrane domain of IST2 is homologous to the TMEM16 family and acts as a constitutively active lipid scramblase. The extended C terminus binds to the plasma membrane and the phosphatidylserine-phosphatidylinositol 4-phosphate exchanger OSH6. Through cellular growth assays and biochemical and structural studies, we characterized the interaction between both proteins and show that OSH6 remains associated with IST2 during lipid shuttling between membranes. These results highlight the role of the IST2-OSH6 complex in lipid trafficking and offer initial insights into the relevance of scramblases for carrier-like lipid transport mechanisms. PubMed: 40866577DOI: 10.1038/s41594-025-01660-z PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.84 Å) |
Structure validation
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