EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Interactions between TTYH2 and APOE facilitate endosomal lipid transfer.
ジャーナル・号・ページ	Nature, Year 2025
掲載日	2025年6月25日
著者	Anastasiia Sukalskaia / Andreas Karner / Anna Pugnetti / Florian Weber / Birgit Plochberger / Raimund Dutzler /
PubMed 要旨	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 ...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.
リンク	Nature / PubMed:40562935
手法	EM (単粒子)
解像度	2.74 - 13.64 Å
構造データ	51106 9g6x EMDB-51106, PDB-9g6x: Cryo-EM structure of TTYH2 in complex with sybody 1 in GDN 手法: EM (単粒子) / 解像度: 3.7 Å 51108 9g71 EMDB-51108, PDB-9g71: Cryo-EM structure of TTYH2 in complex with lipids in GDN 手法: EM (単粒子) / 解像度: 2.74 Å 53249 9qnr EMDB-53249, PDB-9qnr: Cryo-EM structure of TTYH3 in GDN after incubation with ApoE, map2 手法: EM (単粒子) / 解像度: 2.91 Å EMDB-53271: ApoE lipoprotein disc, map3 手法: EM (単粒子) / 解像度: 13.64 Å EMDB-53272: ApoE lipoprotein disc, map1 手法: EM (単粒子) / 解像度: 7.54 Å EMDB-53273: ApoE lipoprotein disc, map2 手法: EM (単粒子) / 解像度: 9.54 Å EMDB-53290: TTYH2 in complex with sybody 2 in GDN 手法: EM (単粒子) / 解像度: 4.26 Å EMDB-53291: TTYH2 in complex with sybody 1 in cell-derived vesicles 手法: EM (単粒子) / 解像度: 8.23 Å EMDB-53292: TTYH2 in complex with lipidated ApoE in cell-derived vesicles 手法: EM (単粒子) / 解像度: 10.71 Å
化合物	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン ChemComp-PLC: DIUNDECYL PHOSPHATIDYL CHOLINE / O-(1-O,2-O-ジドデカノイル-L-グリセロ-3-ホスホ)コリン / リン脂質YM ChemComp-CLR: CHOLESTEROL / コレステロ-ル ChemComp-CPL: 1-PALMITOYL-2-LINOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE / リン脂質YM
由来	vicugna pacos (アルパカ) homo sapiens (ヒト) synthetic construct (人工物)
キーワード	MEMBRANE PROTEIN / complex / sybody / nanobody / TTYH2 / lipid interactions