8AXW
The structure of mouse AsterC (GramD1c) with Ezetimibe
Summary for 8AXW
| Entry DOI | 10.2210/pdb8axw/pdb |
| Descriptor | Protein Aster-C, GLYCEROL, ETHANOL, ... (7 entities in total) |
| Functional Keywords | cholesterol, plasma membrane, endoplasmic reticulum, lipid transport |
| Biological source | Mus musculus (house mouse) |
| Total number of polymer chains | 1 |
| Total formula weight | 27176.09 |
| Authors | Fairall, L.,Xiao, X.,Burger, L.,Tontonoz, P.,Schwabe, J.W.R. (deposition date: 2022-09-01, release date: 2023-09-13, Last modification date: 2024-03-20) |
| Primary citation | 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 Cited by 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: 37943936DOI: 10.1126/science.adf0966 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.6 Å) |
Structure validation
Download full validation report
