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Cited by 68Cholesterol and Lipid MetabolismLipoproteins and Cardiovascular HealthProtein Structure and Dynamics

Versatility in ligand recognition by LDL receptor family proteins: advances and frontiers

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Blacklow, Stephen C·2007·Current Opinion in Structural Biology
DOI 10.1016/j.sbi.2007.08.017PMC PMC2766800
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Abstract

Proteins of the low-density lipoprotein receptor family transport cholesterol-carrying particles into cells, clear protease-inhibitor complexes from the circulation, participate in biological signaling cascades, and even serve as viral receptors. These receptors utilize clusters of cysteine-rich LDL receptor type-A (LA) modules to bind many of their ligands. Recent structures show that these modules typically exhibit a characteristic binding mode to recognize their partners, relying primarily on electrostatic complementarity and avidity effects. The dominant contribution of electrostatic interactions with small interface areas in these complexes allows binding to be regulated by changes in pH via at least two distinct mechanisms. The structure of the subtilisin/kexin family protease PCSK9, a newly identified molecular partner of the LDLR also implicated in LDL-cholesterol homeostasis, also raises the possibility that the LDLR and its related family members may employ other strategies for pH-sensitive binding that have yet to be uncovered.

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  • Considerable conformational differences exist between lipid-free and lipid-bound forms of apoE.

    “Since considerable conformational differences exist between lipid-free and lipid-bound forms of apoE (Blacklow, 2007), the presence of lipids leads to alterations in the binding properties of apoE with Aβ as well as other proteins (Dergunov et al., 2000; Ljungberg et al., 2003).”

    From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Blacklow, 2007

  • Association of apoE with lipid is required for its high-affinity binding to LDLR.

    “Association of apoE with lipid is required for its high-affinity binding to LDLR (Blacklow, 2007).”

    From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Blacklow, 2007

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Research works printed but not linked: 34

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Authors
Blacklow, S. C.
Affiliations
Brigham and Women's Hospital (US)
Corresponding author
Blacklow, Stephen C
ORCID
Blacklow, Stephen C
Venue
Current Opinion in Structural Biology
Publisher
Elsevier BV
Published
2007-08
Volume
17
Issue
4
Pages
419-426
ISSN
0959-440X (ISSN-L)
DOI
10.1016/j.sbi.2007.08.017
PMC
PMC2766800
OpenAlex
W2101101564
Cited by
68
References
2
Citations by year
2026: 5 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 1 · 2020: 2 · 2018: 5 · 2017: 3 · 2016: 5 · 2015: 3 · 2014: 3 · 2013: 4 · 2012: 6
FWCI
4.75
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Current Opinion in Structural Biology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (HL-61001, R01HL061001)
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 › Protein Structure and Dynamics
Keywords
LDL receptor family, ligand recognition, cysteine-rich domain, electrostatic complementarity, avidity effects, PCSK9, protease-inhibitor complex, viral receptor, cholesterol absorption, receptor structure
MeSH terms
Proprotein Convertase 9, Animals, Apolipoproteins, Binding Sites, Histidine, Humans, Hydrogen-Ion Concentration, Ligands, Models, Molecular, Protein Conformation, Receptors, LDL, Serine Endopeptidases, Crystallography, X-Ray, LDL-Receptor Related Protein-Associated Protein, Proprotein Convertases

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