ArticleBiochemistry2012
Contributions of a disulfide bond and a reduced cysteine side chain to the intrinsic activity of the high-density lipoprotein receptor SR-BI.
Article in Biochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 42 citations in OpenAlex.
- Identification of scavenger receptor BI as a scavenger of free heme that is essential for protection against hemolysis.Nature communications · 2026Article
- High-density lipoprotein cholesterol: how studying the 'good cholesterol' could improve cardiovascular health.Open biology · 2025Review
- Modulation of Mitochondria-Endoplasmic Reticulum Contacts (MERCs) by Small Molecules as a New Strategy for Restoring Lipid Metabolism in an Amyotrophic Lateral Sclerosis Model.Journal of medicinal chemistry · 2025Article
- CD36 as a Therapeutic Target in Tumor Microenvironment and Lipid Metabolism.Anti-cancer agents in medicinal chemistry · 2025Review
- The contribution of mitochondria-associated ER membranes to cholesterol homeostasis.bioRxiv : the preprint server for biology · 2024Article
- The Absorption, Storage, and Transport of Ocular Carotenoids and Retinoids.Annual review of vision science · 2024Review
- Review
- Review
- Mechanism for the selective uptake of macular carotenoids mediated by the HDL cholesterol receptor SR-BI.Experimental eye research · 2023Article
- Different Pathways of Cellular Cholesterol Efflux.Cell biochemistry and biophysics · 2022Review
- SR-B1's Next Top Model: Structural Perspectives on the Functions of the HDL Receptor.Current atherosclerosis reports · 2022Review
- Expression and biochemical analyses of proteins involved in the transport of carotenoids and retinoids.Methods in enzymology · 2022Article
- Internalization and Transport of PEGylated Lipid-Based Mixed Micelles across Caco-2 Cells Mediated by Scavenger Receptor B1.Pharmaceutics · 2021Article
- Molecular components affecting ocular carotenoid and retinoid homeostasis.Progress in retinal and eye research · 2021Review
- The molecular aspects of absorption and metabolism of carotenoids and retinoids in vertebrates.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2020Review
- Carotenoid metabolism at the intestinal barrier.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2020Review
- Maize 16-kD γ-zein forms very unusual disulfide-bonded polymers in the endoplasmic reticulum: implications for prolamin evolution.Journal of experimental botany · 2018Article
- Scavenger receptor B type 1: expression, molecular regulation, and cholesterol transport function.Journal of lipid research · 2018Review
- Intestinal CD36 and Other Key Proteins of Lipid Utilization: Role in Absorption and Gut Homeostasis.Comprehensive Physiology · 2018Review
- SR-B1: A Unique Multifunctional Receptor for Cholesterol Influx and Efflux.Annual review of physiology · 2018Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The high-density lipoprotein (HDL) receptor scavenger receptor class B, type I (SR-BI), binds HDL and mediates selective cholesteryl ester uptake. SR-BI's structure and mechanism are poorly understood. We used mass spectrometry to assign the two disulfide bonds in SR-BI that connect cysteines within the conserved Cys(321)-Pro(322)-Cys(323) (CPC) motif and connect Cys(280) to Cys(334). We used site-specific mutagenesis to evaluate the contributions of the CPC motif and the side chain of extracellular Cys(384) to HDL binding and lipid uptake. The effects of CPC mutations on activity were context-dependent. Full wild-type (WT) activity required Pro(322) and Cys(323) only when Cys(321) was present. Reduced intrinsic activities were observed for CXC and CPX, but not XXC, XPX, or XXX mutants (X ≠ WT residue). Apparently, a free thiol side chain at position 321 that cannot form an intra-CPC disulfide bond with Cys(323) is deleterious, perhaps because of aberrant disulfide bond formation. Pro(322) may stabilize an otherwise strained CPC disulfide bond, thus supporting WT activity, but this disulfide bond is not absolutely required for normal activity. C(384)X (X = S, T, L, Y, G, or A) mutants exhibited altered activities that varied with the side chain's size: larger side chains phenocopied WT SR-BI treated with its thiosemicarbazone inhibitor BLT-1 (enhanced binding, weakened uptake); smaller side chains produced almost inverse effects (increased uptake:binding ratio). C(384)X mutants were BLT-1-resistant, supporting the proposal that Cys(384)'s thiol interacts with BLT-1. We discuss the implications of our findings on the functions of the extracellular loop cysteines in SR-BI and compare our results to those presented by other laboratories.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.