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Cryo-EM structures of NPC1L1 reveal mechanisms of cholesterol transport and ezetimibe inhibition
Abstract
Details of intestinal sterol absorption and inhibition by cholesterol-lowering drug are uncovered in new protein structures.
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Structural analyses have revealed that the N-terminal domain of NPC1L1 possesses a cavity that accommodates cholesterol.
“Structural analyses have revealed that the N-terminal domain of NPC1L1 possesses a cavity that accommodates cholesterol (14–16).”
From Aster-dependent nonvesicular transport facilitates dietary cholesterol uptake (2023) · cites this paper as [15]
Ezetimibe blocks the channel within NPC1L1 required for cholesterol deposition into the plasma membrane.
“EZ blocks the channel within NPC1L1 required for cholesterol deposition into the PM (15).”
From Aster-dependent nonvesicular transport facilitates dietary cholesterol uptake (2023) · cites this paper as [15]
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Heart Disease and Stroke Statistics—2023 Update: A Report From the American Heart Association
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Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes
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Inactivating Mutations in NPC1L1 and Protection from Coronary Heart Disease
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Sorted by citations
A structure of human Scap bound to Insig-2 suggests how their interaction is regulated by sterols
Yan, R., Cao, P., Song, W., Qian, H., Du, X., Coates, H. W., Zhao, X., Li, Y., Gao, S., Gong, X., et al. (2021) · Science · doi:10.1126/science.abb2224 · Cited by 100
Aster-dependent nonvesicular transport facilitates dietary cholesterol uptake
Ferrari, A., Whang, E., Xiao, X., Kennelly, J. P., Romartinez-Alonso, B., Mack, J. J., Weston, T., Chen, K., Kim, Y., Tol, M. J., et al. (2023) · Science · doi:10.1126/science.adf0966 · Cited by 61
Metadata
- Authors
- Huang, C.-S., Yu, X., Fordstrom, P., Choi, K., Chung, B. C., Roh, S.-H., Chiu, W., Zhou, M., Min, X., & Wang, Z.
- Affiliations
- Department of Therapeutic Discovery, Amgen Research, Amgen Inc., 1120 Veterans Blvd., South San Francisco, CA 94080, USA.
- Department of Cardiometabolic Disorders, Amgen Research, Amgen Inc., 1120 Veterans Blvd., South San Francisco, CA 94080, USA.
- Department of Bioengineering and James H. Clark Center, Stanford University, Stanford, CA 94305, USA.
- Venue
- Science Advances
- Published
- 2020-06-17
- Volume
- 6
- Issue
- 25
- ISSN
- 2375-2548
- PMC
- PMC7304964
- Cited by
- 98
- References
- 5
- Language
- en
- Funders
- National Institutes of Health (P41GM103832)
- National Research Foundation (2019R1C1C004598, 2019R1A6A7076042)
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