+検索条件
-Structure paper
タイトル | Structural Basis of Low-pH-Dependent Lysosomal Cholesterol Egress by NPC1 and NPC2. |
---|---|
ジャーナル・号・ページ | Cell, Vol. 182, Issue 1, Page 98-111.e18, Year 2020 |
掲載日 | 2020年7月9日 |
著者 | Hongwu Qian / Xuelan Wu / Ximing Du / Xia Yao / Xin Zhao / Joyce Lee / Hongyuan Yang / Nieng Yan / |
PubMed 要旨 | Lysosomal cholesterol egress requires two proteins, NPC1 and NPC2, whose defects are responsible for Niemann-Pick disease type C (NPC). Here, we present systematic structural characterizations that ...Lysosomal cholesterol egress requires two proteins, NPC1 and NPC2, whose defects are responsible for Niemann-Pick disease type C (NPC). Here, we present systematic structural characterizations that reveal the molecular basis for low-pH-dependent cholesterol delivery from NPC2 to the transmembrane (TM) domain of NPC1. At pH 8.0, similar structures of NPC1 were obtained in nanodiscs and in detergent at resolutions of 3.6 Å and 3.0 Å, respectively. A tunnel connecting the N-terminal domain (NTD) and the transmembrane sterol-sensing domain (SSD) was unveiled. At pH 5.5, the NTD exhibits two conformations, suggesting the motion for cholesterol delivery to the tunnel. A putative cholesterol molecule is found at the membrane boundary of the tunnel, and TM2 moves toward formation of a surface pocket on the SSD. Finally, the structure of the NPC1-NPC2 complex at 4.0 Å resolution was obtained at pH 5.5, elucidating the molecular basis for cholesterol handoff from NPC2 to NPC1(NTD). |
リンク | Cell / PubMed:32544384 |
手法 | EM (単粒子) |
解像度 | 3.0 - 4.0 Å |
構造データ | EMDB-21545, PDB-6w5r: EMDB-21546, PDB-6w5s: EMDB-21547, PDB-6w5t: EMDB-21548, PDB-6w5u: EMDB-21549, PDB-6w5v: |
化合物 | ChemComp-NAG: ChemComp-CLR: ChemComp-POV: |
由来 |
|
キーワード | TRANSPORT PROTEIN / Cholesterol Lysosome |