ジャーナル: Cell / 年: 2020 タイトル: Structural Basis of Low-pH-Dependent Lysosomal Cholesterol Egress by NPC1 and NPC2. 著者: Hongwu Qian / Xuelan Wu / Ximing Du / Xia Yao / Xin Zhao / Joyce Lee / Hongyuan Yang / Nieng Yan / 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).
NPC intracellular cholesterol transporter ... , 2種, 2分子 AD
#1: タンパク質
NPCintracellularcholesteroltransporter1 / Niemann-Pick C1 protein
分子量: 146083.688 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: NPC1 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: O15118
#2: タンパク質
NPCintracellularcholesteroltransporter2 / Epididymal secretory protein E1 / Human epididymis-specific protein 1 / He1 / Niemann-Pick disease ...Epididymal secretory protein E1 / Human epididymis-specific protein 1 / He1 / Niemann-Pick disease type C2 protein
分子量: 17932.600 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: NPC2, HE1 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P61916