The LDL receptor: how acid pulls the trigger
Abstract
The low-density lipoprotein receptor normally carries lipoprotein particles into cells, and releases them upon delivery to the low pH milieu of the endosome. Recent structural and functional studies of the receptor, combined with the plethora of prior knowledge about normal receptor function and the effects of disease-associated mutations that cause familial hypercholesterolemia, reveal a detailed molecular model for how the acidic environment of the endosome triggers the release of bound lipoprotein particles. Remarkably, the receptor dynamically interconverts between open (ligand-active) and closed (ligand-inactive) conformations in response to pH, relying on a specific arrangement of fixed and flexible interdomain connections to facilitate efficient binding and release of its lipoprotein ligands.
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LDLR primarily mediates lipid metabolism.
“LDLR, which primarily mediates lipid metabolism50.”
From Decreased lipidated ApoE‐receptor interactions confer protection against pathogenicity of ApoE and its lipid cargoes in lysosomes (2025) · cites this paper as [50]
Cites
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Three-Dimensional Structure of the LDL Receptor-Binding Domain of Human Apolipoprotein E
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An essential receptor for adeno-associated virus infection
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- Authors
- Beglova, N., & Blacklow, S. C.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Blacklow, Stephen C.
- ORCID
- Blacklow, Stephen C.
- Venue
- Trends in Biochemical Sciences
- Publisher
- Elsevier BV
- Published
- 2005-06
- Volume
- 30
- Issue
- 6
- Pages
- 309-317
- ISSN
- 0968-0004 (ISSN-L)
- OpenAlex
- W1974633998
- Cited by
- 120
- References
- 2
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 5 · 2023: 1 · 2022: 2 · 2021: 10 · 2020: 2 · 2019: 9 · 2018: 6 · 2017: 7 · 2016: 9 · 2015: 5 · 2014: 5 · 2013: 3 · 2012: 6
- FWCI
- 1.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Biochemical Sciences (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Keywords
- LDL receptor, low-density lipoprotein, endosomal acidification, receptor conformational change, ligand dissociation, receptor structure, lipoprotein uptake
- MeSH terms
- Binding Sites, Epidermal Growth Factor, Humans, Hydrogen-Ion Concentration, Hyperlipoproteinemia Type II, Mutation, Receptors, LDL, Endosomes, Structure-Activity Relationship, Protein Structure, Tertiary
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