ArticleThe Journal of biological chemistry2015
Generation of a Potent Low Density Lipoprotein Receptor-related Protein 1 (LRP1) Antagonist by Engineering a Stable Form of the Receptor-associated Protein (RAP) D3 Domain.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Integrative bioinformatics frameworks for abdominal aortic aneurysm using GWAS meta-analysis, biological network construction, and structural modeling.Scientific reports · 2025Pooled it
- High-Throughput Screening Identifies Small-Molecule Inhibitors of the Tau-LRP1 Interaction.bioRxiv : the preprint server for biology · 2026Article
- Neuroproteasomes regulate endogenous tau paired helical filament formation in an APOE genotype- and age-dependent manner.Nature neuroscience · 2026Article
- Rift Valley fever virus infects trophoblast cell lines in an LRP1-dependent manner.The Journal of general virology · 2026Article
- Article
- Alpha-1 antitrypsin-glucocorticoid receptor axis: a new pathway in immune modulation.Molecular medicine (Cambridge, Mass.) · 2026Article
- Tracking tau and cellular responses in human iPSC-microglia: from uptake to seedable secretion, including in extracellular vesicles.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Engineered platelets as targeted protein degraders and application to breast cancer models.Nature biotechnology · 2025Article
- Sodium-Glucose Cotransporter Inhibition Preserves Apolipoprotein M During Acute Inflammation in Mice and Humans.JACC. Advances · 2025Article
- Targeting A2M-LRP1 reverses uterine spiral artery remodeling disorder and alleviates the progression of preeclampsia.Cell communication and signaling : CCS · 2025Article
- Functions for platelet factor 4 (PF4/CXCL4) and its receptors in fibroblast-myofibroblast transition and fibrotic failure of arteriovenous fistulas (AVFs).The journal of vascular access · 2024Article
- Article
- Receptor-associated protein impairs ligand binding to megalin and megalin-dependent endocytic flux in proximal tubule cells.American journal of physiology. Renal physiology · 2023Article
- Secreted LRPAP1 binds and triggers IFNAR1 degradation to facilitate virus evasion from cellular innate immunity.Signal transduction and targeted therapy · 2023Article
- Targeted Lysosomal Degradation of Secreted and Cell Surface Proteins through the LRP-1 Pathway.Journal of the American Chemical Society · 2023Article
- LRP-1 links post-translational modifications to efficient presentation of celiac disease-specific T cell antigens.Cell chemical biology · 2023Article
- Article
- The multifaceted role of plasminogen in inflammation.Cellular signalling · 2020Review
- Cell-based artificial APC resistant to lentiviral transduction for efficient generation of CAR-T cells from various cell sources.Journal for immunotherapy of cancer · 2020Article
- The low density receptor-related protein 1 plays a significant role in ricin-mediated intoxication of lung cells.Scientific reports · 2020Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The low density lipoprotein receptor-related protein 1 (LRP1) is a member of the low density lipoprotein receptor family and plays important roles in a number of physiological and pathological processes. Expression of LRP1 requires the receptor-associated protein (RAP), a molecular chaperone that binds LRP1 and other low density lipoprotein receptor family members in the endoplasmic reticulum and traffics with them to the Golgi where the acidic environment causes its dissociation. Exogenously added RAP is a potent LRP1 antagonist and binds to LRP1 on the cell surface, preventing ligands from binding. Following endocytosis, RAP dissociates in the acidic endosome, allowing LRP1 to recycle back to the cell surface. The acid-induced dissociation of RAP is mediated by its D3 domain, a relatively unstable three-helical bundle that denatures at pH <6.2 due to protonation of key histidine residues on helices 2 and 3. To develop an LRP1 inhibitor that does not dissociate at low pH, we introduced a disulfide bond between the second and third helices in the RAP D3 domain. By combining this disulfide bond with elimination of key histidine residues, we generated a stable RAP molecule that is resistant to both pH- and heat-induced denaturation. This molecule bound to LRP1 with high affinity at both neutral and acidic pH and proved to be a potent inhibitor of LRP1 function both in vitro and in vivo, suggesting that our stable RAP molecule may be useful in multiple pathological settings where LRP1 blockade has been shown to be effective.
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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.