ArticleThe Journal of biological chemistry2012
Characterization of the interaction of sclerostin with the low density lipoprotein receptor-related protein (LRP) family of Wnt co-receptors.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 95 citations in OpenAlex.
- Blocking interaction of sclerostin loop3 with osteoblastic LRP4 counteracts bone loss without increasing arterial stiffness during mechanical unloading.Journal of orthopaedic translation · 2026Article
- Osteoblastic sclerostin loop3-LRP4 interaction required by sclerostin to inhibit bone formation.Bone research · 2026Article
- Sclerostin in Vascular Calcification: Hypoxia-Driven Regulation and Therapeutic Modulation by Natural Products.Current atherosclerosis reports · 2026Review
- Sclerostin deficiency sensitizes white adipocytes to thermogenic signals that induce beiging in mice.Nature communications · 2026Article
- Mapping the sclerostin-LRP4 binding interface identifies critical interaction hotspots in loops 1 and 3 of sclerostin.FEBS letters · 2025Article
- In silico design of novel precision vaccine targeting sclerostin epitopes for osteoporosis prevention and treatment.Frontiers in immunology · 2025Article
- Activation of Wnt signaling in human fracture callus and nonunion tissues.Bone reports · 2024Article
- Wnt/β-catenin signaling components and mechanisms in bone formation, homeostasis, and disease.Bone research · 2024Review
- Sclerostin inhibition in rare bone diseases: Molecular understanding and therapeutic perspectives.Journal of orthopaedic translation · 2024Review
- Evolutionary and functional analyses of LRP5 in archaic and extant modern humans.Human genomics · 2024Article
- Novel mutation in LRP5 gene cause rare osteosclerosis: cases studies and literature review.Molecular genetics and genomics : MGG · 2023Review
- Endocrine Functions of Sclerostin.Current opinion in endocrine and metabolic research · 2023Article
- Directed evolution identifies high-affinity cystine-knot peptide agonists and antagonists of Wnt/β-catenin signaling.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Importance of Sclerostin as Bone-Muscle Mediator Crosstalk.Annals of geriatric medicine and research · 2022Article
- Drug discovery of sclerostin inhibitors.Acta pharmaceutica Sinica. B · 2022Review
- Positive and Negative Regulators of Sclerostin Expression.International journal of molecular sciences · 2022Review
- Competitive blocking of LRP4-sclerostin binding interface strongly promotes bone anabolic functions.Cellular and molecular life sciences : CMLS · 2022Article
- Characterization of sclerostin's response within white adipose tissue to an obesogenic diet at rest and in response to acute exercise in male mice.Frontiers in physiology · 2022Article
- Article
- Conformational Dynamics of Sclerostin-LRP6 Complex Analyzed by HDX-MS.Biomolecules & therapeutics · 2021Article
Corrections and comments
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Authors and funding
20 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
LRP5 and LRP6 are proteins predicted to contain four six-bladed β-propeller domains and both bind the bone-specific Wnt signaling antagonist sclerostin. Here, we report the crystal structure of the amino-terminal region of LRP6 and using NMR show that the ability of sclerostin to bind to this molecule is mediated by the central core of sclerostin and does not involve the amino- and carboxyl-terminal flexible arm regions. We show that this structured core region interacts with LRP5 and LRP6 via an NXI motif (found in the sequence PNAIG) within a flexible loop region (loop 2) within the central core region. This sequence is related closely to a previously identified motif in laminin that mediates its interaction with the β-propeller domain of nidogen. However, the NXI motif is not involved in the interaction of sclerostin with LRP4 (another β-propeller containing protein in the LRP family). A peptide derived from the loop 2 region of sclerostin blocked the interaction of sclerostin with LRP5/6 and also inhibited Wnt1 but not Wnt3A or Wnt9B signaling. This suggests that these Wnts interact with LRP6 in different ways.
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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.