ArticleBiochemistry2010
Structural insight into the role of thrombospondin-1 binding to calreticulin in calreticulin-induced focal adhesion disassembly.
Article in Biochemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 39 citations in OpenAlex.
- Immunomodulatory role and therapeutic potential of thrombospondin-1 during infectious diseases and autoimmunity.BMC biology · 2026Review
- The Role of Thrombospondin-2 in Myocardial Fibrosis.Drug design, development and therapy · 2026Review
- Thrombospondin 1 Promotes Cytoskeleton Remodeling, Dedifferentiation, and Pulmonary Metastasis through ITGA1 and ITGA6 in Osteosarcoma.International journal of biological sciences · 2025Article
- Emerging functions of thrombospondin-1 in immunity.Seminars in cell & developmental biology · 2024Review
- Thrombospondin-1 Signaling Through the Calreticulin/LDL Receptor Related Protein 1 Axis: Functions and Possible Roles in Glaucoma.Frontiers in cell and developmental biology · 2022Review
- Vitamin D3 and its hydroxyderivatives as promising drugs against COVID-19: a computational study.Journal of biomolecular structure & dynamics · 2022Article
- Functions of Thrombospondin-1 in the Tumor Microenvironment.International journal of molecular sciences · 2021Review
- Role of thrombospondin‑1 and thrombospondin‑2 in cardiovascular diseases (Review).International journal of molecular medicine · 2020Review
- Thrombospondin 1 (THBS1) Promotes Follicular Angiogenesis, Luteinization, and Ovulation in Primates.Frontiers in endocrinology · 2019Article
- Neurodegenerative Disease-Associated Variants in TREM2 Destabilize the Apical Ligand-Binding Region of the Immunoglobulin Domain.Frontiers in neurology · 2019Article
- Dissecting physical structure of calreticulin, an intrinsically disordered CaJournal of biomolecular structure & dynamics · 2018Article
- The role of the endoplasmic reticulum protein calreticulin in mediating TGF-β-stimulated extracellular matrix production in fibrotic disease.Journal of cell communication and signaling · 2018Review
- Thrombospondin-1 promotes cell migration, invasion and lung metastasis of osteosarcoma through FAK dependent pathway.Oncotarget · 2017Article
- Thrombospondins: A Role in Cardiovascular Disease.International journal of molecular sciences · 2017Review
- Activation mechanisms of αVβ3 integrin by binding to fibronectin: A computational study.Protein science : a publication of the Protein Society · 2017Article
- Association of calreticulin expression with disease activity and organ damage in systemic lupus erythematosus patients.Experimental and therapeutic medicine · 2017Article
- PEDF increases the tumoricidal activity of macrophages towards prostate cancer cells in vitro.PloS one · 2017Article
- Calreticulin: Challenges Posed by the Intrinsically Disordered Nature of Calreticulin to the Study of Its Function.Frontiers in cell and developmental biology · 2017Article
- Structural Insight for Roles of DR5 Death Domain Mutations on Oligomerization of DR5 Death Domain-FADD Complex in the Death-Inducing Signaling Complex Formation: A Computational Study.Journal of molecular modeling · 2016Article
- Characterization of calmodulin-Fas death domain interaction: an integrated experimental and computational study.Biochemistry · 2014Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Thrombospondin-1 (TSP1) binding to calreticulin (CRT) on the cell surface stimulates association of CRT with LDL receptor-related protein (LRP1) to signal focal adhesion disassembly and engagement of cellular activities. The structural basis for this phenomenon is unknown. We studied the binding thermodynamics of the TSP1-CRT complex and the conformational changes in CRT induced by binding to TSP1 with combined binding free energy analysis, molecular dynamics simulation, and anisotropic network model restrained molecular dynamics simulation. Results showed that mutations of Lys 24 and Lys 32 in TSP1 to Ala and of amino acids 24-26 and 32-34 in CRT to Ala significantly weakened the binding of TSP1 and CRT, which is consistent with experimental results. Upon validation of the calculated binding affinity changes of the TSP1-CRT complex by mutations in key residues in TSP1 and CRT with the experimental results, we performed conformational analyses to understand the role of TSP1 binding to CRT in the induction of conformational changes in CRT. Conformational analyses showed that TSP1 binding to CRT resulted in a more "open" conformation and a significant rotational change for the CRT N-domain with respect to the CRT P-domain, which could expose the potential binding site(s) in CRT for binding to LRP1 to signal focal adhesion disassembly. Results offer structural insight into the role of TSP1 binding to CRT in CRT-induced focal adhesion disassembly.
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Registered trials
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