8AXW

The structure of mouse AsterC (GramD1c) with Ezetimibe

8AXW の概要

• エントリーDOI: 10.2210/pdb8axw/pdb
• 分子名称: Protein Aster-C, GLYCEROL, ETHANOL, ... (7 entities in total)
• 機能のキーワード: cholesterol, plasma membrane, endoplasmic reticulum, lipid transport
• 由来する生物種: Mus musculus (house mouse)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 27176.09

構造登録者

Fairall, L.,Xiao, X.,Burger, L.,Tontonoz, P.,Schwabe, J.W.R. (登録日: 2022-09-01, 公開日: 2023-09-13, 最終更新日: 2024-03-20)

主引用文献

Ferrari, A.,Whang, E.,Xiao, X.,Kennelly, J.P.,Romartinez-Alonso, B.,Mack, J.J.,Weston, T.,Chen, K.,Kim, Y.,Tol, M.J.,Bideyan, L.,Nguyen, A.,Gao, Y.,Cui, L.,Bedard, A.H.,Sandhu, J.,Lee, S.D.,Fairall, L.,Williams, K.J.,Song, W.,Munguia, P.,Russell, R.A.,Martin, M.G.,Jung, M.E.,Jiang, H.,Schwabe, J.W.R.,Young, S.G.,Tontonoz, P.
Aster-dependent nonvesicular transport facilitates dietary cholesterol uptake.
Science, 382:eadf0966-eadf0966, 2023

PubMed Abstract: Intestinal absorption is an important contributor to systemic cholesterol homeostasis. Niemann-Pick C1 Like 1 (NPC1L1) assists in the initial step of dietary cholesterol uptake, but how cholesterol moves downstream of NPC1L1 is unknown. We show that Aster-B and Aster-C are critical for nonvesicular cholesterol movement in enterocytes. Loss of NPC1L1 diminishes accessible plasma membrane (PM) cholesterol and abolishes Aster recruitment to the intestinal brush border. Enterocytes lacking Asters accumulate PM cholesterol and show endoplasmic reticulum cholesterol depletion. Aster-deficient mice have impaired cholesterol absorption and are protected against diet-induced hypercholesterolemia. Finally, the Aster pathway can be targeted with a small-molecule inhibitor to manipulate cholesterol uptake. These findings identify the Aster pathway as a physiologically important and pharmacologically tractable node in dietary lipid absorption.

PubMed: 37943936
DOI: 10.1126/science.adf0966

実験手法

X-RAY DIFFRACTION (1.6 Å)