Journal
NATURE COMMUNICATIONS
Volume 11, Issue 1, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-020-16288-4
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Funding
- Electron microscopy laboratory
- Cryo-EM platform of Peking University
- Ministry of Science and Technology of China (National Key RAMP
- D Program of China) [2016YFA0502004]
- National Natural Science Foundation of China [91957201, 31622021, 31870833, 31821091, 31521004, 21672011, 21822101, 31900859]
- Beijing Natural Science Foundation [5192009]
- Young Thousand Talents Program of China
- NIH grant in U.S.A. [R01 AG063544]
- China Postdoctoral Science Foundation [2016M600856, 2017T100014, 2019M650324, 2019T120014]
- Boya Postdoctoral Fellowship
- Peking-Tsinghua Center for Life Sciences Postdoctoral Fellowship of Peking University
- Boehringer-Ingelheim
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Sterol O-acyltransferase 1 (SOAT1) is an endoplasmic reticulum (ER) resident, multi-transmembrane enzyme that belongs to the membrane-bound O-acyltransferase (MBOAT) family. It catalyzes the esterification of cholesterol to generate cholesteryl esters for cholesterol storage. SOAT1 is a target to treat several human diseases. However, its structure and mechanism remain elusive since its discovery. Here, we report the structure of human SOAT1 (hSOAT1) determined by cryo-EM. hSOAT1 is a tetramer consisted of a dimer of dimer. The structure of hSOAT1 dimer at 3.5 angstrom resolution reveals that a small molecule inhibitor CI-976 binds inside the catalytic chamber and blocks the accessibility of the active site residues H460, N421 and W420. Our results pave the way for future mechanistic study and rational drug design targeting hSOAT1 and other mammalian MBOAT family members. Sterol O-acyltransferase 1 (SOAT1, also named ACAT1) is an endoplasmic reticulum resident enzyme which catalyzes the esterification of cholesterol to generate cholesteryl esters. Here, authors report cryo-EM structures of human SOAT1 which reveal the binding site of the competitive inhibitor CI-976.
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