9G71

Cryo-EM structure of TTYH2 in complex with lipids in GDN

9G71 の概要

• エントリーDOI: 10.2210/pdb9g71/pdb
• 関連するPDBエントリー: 7p54
• EMDBエントリー: 51108
• 分子名称: 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)
• 機能のキーワード: complex, sybody, nanobody, ttyh2, membrane protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 149764.80

構造登録者

Sukalskaia, A.,Weber, F.,Plochberger, B.,Dutzler, R. (登録日: 2024-07-19, 公開日: 2025-05-21, 最終更新日: 2025-07-09)

主引用文献

Sukalskaia, A.,Karner, A.,Pugnetti, A.,Weber, F.,Plochberger, B.,Dutzler, R.
Interactions between TTYH2 and APOE facilitate endosomal lipid transfer.
Nature, 2025

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: 40562935
DOI: 10.1038/s41586-025-09200-x

実験手法

ELECTRON MICROSCOPY (2.74 Å)