9G71
Cryo-EM structure of TTYH2 in complex with lipids in GDN
Summary for 9G71
| Entry DOI | 10.2210/pdb9g71/pdb |
| Related | 7p54 |
| EMDB information | 51108 |
| Descriptor | Protein tweety homolog 2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total) |
| Functional Keywords | complex, sybody, nanobody, ttyh2, membrane protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 149764.80 |
| Authors | Sukalskaia, A.,Weber, F.,Plochberger, B.,Dutzler, R. (deposition date: 2024-07-19, release date: 2025-05-21, Last modification date: 2025-07-09) |
| Primary citation | Sukalskaia, A.,Karner, A.,Pugnetti, A.,Weber, F.,Plochberger, B.,Dutzler, R. Interactions between TTYH2 and APOE facilitate endosomal lipid transfer. Nature, 2025 Cited by PubMed Abstract: The Tweety homologues (TTYHs) constitute a family of eukaryotic membrane proteins that, on the basis of structural features, were recently proposed to contribute to lipid transfer between soluble carriers and cellular membranes. However, in the absence of supporting data, this function was hypothetical. Here through pull-down of endogenous proteins, we identify APOE as the interaction partner of human TTYH2. Subcellular fractionation and immunocytochemistry assays showed that both proteins colocalize in endosomal compartments. Characterization of the specific interaction between APOE and TTYH2 through binding assays and structural studies enabled us to identify an epitope in an extended domain of TTYH2 that faces the endosomal lumen. Structures of complexes with APOE-containing lipoprotein particles revealed a binding mode that places lipids in a suitable position to facilitate their diffusion into the membrane. Moreover, in vitro studies revealed that lipid transfer is accelerated by TTYH2. Collectively, our findings indicate that TTYH2 has a role in the unloading of APOE-containing lipoproteins after they are endocytosed. These results define a new protein class that facilitates the extraction of lipids from and their insertion into cellular membranes. Although ubiquitous, this process could be of particular relevance in the brain, where APOE is involved in the transfer of lipids between astrocytes and neurons. PubMed: 40562935DOI: 10.1038/s41586-025-09200-x PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.74 Å) |
Structure validation
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