6GQF

The structure of mouse AsterA (GramD1a) with 25-hydroxy cholesterol

6GQF の概要

• エントリーDOI: 10.2210/pdb6gqf/pdb
• 分子名称: GRAM domain-containing protein 1A, 25-HYDROXYCHOLESTEROL, GLYCEROL (3 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 (Mouse)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 105960.82

構造登録者

Fairall, L.,Gurnett, J.E.,Vashi, D.,Sandhu, J.,Tontonoz, P.,Schwabe, J.W.R. (登録日: 2018-06-07, 公開日: 2018-09-26, 最終更新日: 2024-10-16)

主引用文献

Sandhu, J.,Li, S.,Fairall, L.,Pfisterer, S.G.,Gurnett, J.E.,Xiao, X.,Weston, T.A.,Vashi, D.,Ferrari, A.,Orozco, J.L.,Hartman, C.L.,Strugatsky, D.,Lee, S.D.,He, C.,Hong, C.,Jiang, H.,Bentolila, L.A.,Gatta, A.T.,Levine, T.P.,Ferng, A.,Lee, R.,Ford, D.A.,Young, S.G.,Ikonen, E.,Schwabe, J.W.R.,Tontonoz, P.
Aster Proteins Facilitate Nonvesicular Plasma Membrane to ER Cholesterol Transport in Mammalian Cells.
Cell, 175:514-529.e20, 2018

PubMed Abstract: The mechanisms underlying sterol transport in mammalian cells are poorly understood. In particular, how cholesterol internalized from HDL is made available to the cell for storage or modification is unknown. Here, we describe three ER-resident proteins (Aster-A, -B, -C) that bind cholesterol and facilitate its removal from the plasma membrane. The crystal structure of the central domain of Aster-A broadly resembles the sterol-binding fold of mammalian StARD proteins, but sequence differences in the Aster pocket result in a distinct mode of ligand binding. The Aster N-terminal GRAM domain binds phosphatidylserine and mediates Aster recruitment to plasma membrane-ER contact sites in response to cholesterol accumulation in the plasma membrane. Mice lacking Aster-B are deficient in adrenal cholesterol ester storage and steroidogenesis because of an inability to transport cholesterol from SR-BI to the ER. These findings identify a nonvesicular pathway for plasma membrane to ER sterol trafficking in mammals.

PubMed: 30220461
DOI: 10.1016/j.cell.2018.08.033

実験手法

X-RAY DIFFRACTION (2.9 Å)