ArticleProceedings of the National Academy of Sciences of the United States of America2020
Calcium and hydroxyapatite binding site of human vitronectin provides insights to abnormal deposit formation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Plasma Proteomic Signatures for Alzheimer's Disease: Comparable Accuracy to ATN Biomarkers and Cross-Platform Validation.Annals of clinical and translational neurology · 2026Article
- Structural basis for lipid binding by the blood protein vitronectin, a component of HDL.bioRxiv : the preprint server for biology · 2025Article
- Proteomics of Urinary Extracellular Vesicles Highlight the Involvement of Vitronectin and the Fibrinolytic and TNF Pathways as Mechanisms Underlying Renal Fibrosis in Kidney Transplant Patients.Journal of extracellular biology · 2025Article
- Potential Targeting Mechanisms for Bone-Directed Therapies.International journal of molecular sciences · 2024Review
- Cell-cell communication in kidney fibrosis.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Review
- Solid-state NMR MAS CryoProbe enables structural studies of human blood protein vitronectin bound to hydroxyapatite.Journal of structural biology · 2024Article
- Calpain-specific breakdown fragment in human drusen.Histology and histopathology · 2024Article
- Therapeutic targets for age-related macular degeneration: proteome-wide Mendelian randomization and colocalization analyses.Frontiers in neurology · 2024Article
- Article
- Calcification of Various Bioprosthetic Materials in Rats: Is It Really Different?International journal of molecular sciences · 2023Article
- Macrophage promotes fibroblast activation and kidney fibrosis by assembling a vitronectin-enriched microenvironment.Theranostics · 2023Article
- Calcium-induced environmental adaptability of the blood protein vitronectin.Biophysical journal · 2022Article
- Role of Vitronectin and Its Receptors in Neuronal Function and Neurodegenerative Diseases.International journal of molecular sciences · 2022Review
- Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The human blood protein vitronectin (Vn) is a major component of the abnormal deposits associated with age-related macular degeneration, Alzheimer's disease, and many other age-related disorders. Its accumulation with lipids and hydroxyapatite (HAP) has been demonstrated, but the precise mechanism for deposit formation remains unknown. Using a combination of solution and solid-state NMR experiments, cosedimentation assays, differential scanning fluorimetry (DSF), and binding energy calculations, we demonstrate that Vn is capable of binding both soluble ionic calcium and crystalline HAP, with high affinity and chemical specificity. Calcium ions bind preferentially at an external site, at the top of the hemopexin-like (HX) domain, with a group of four Asp carboxylate groups. The same external site is also implicated in HAP binding. Moreover, Vn acquires thermal stability upon association with either calcium ions or crystalline HAP. The data point to a mechanism whereby Vn plays an active role in orchestrating calcified deposit formation. They provide a platform for understanding the pathogenesis of macular degeneration and other related degenerative disorders, and the normal functions of Vn, especially those related to bone resorption.
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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.