ArticleThe Journal of biological chemistry2018
Proline hydroxylation in collagen supports integrin binding by two distinct mechanisms.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 83 citations in OpenAlex.
- Article
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- Promoting collagen synthesis: a viable strategy to combat skin ageing.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Collagen IV biosynthesis: Intracellular choreography of post-translational modifications.Matrix biology : journal of the International Society for Matrix Biology · 2025Review
- Mass spectrometry reveals age-dependent collagen decline in murine atria.Annals of the New York Academy of Sciences · 2025Article
- Recent Advancements in Marine Collagen: Exploring New Sources, Processing Approaches, and Nutritional Applications.Marine drugs · 2025Review
- Comprehensive analysis of the effects ofFrontiers in cell and developmental biology · 2025Article
- From ductal carcinoma in situ to invasive breast cancer: the prognostic value of the extracellular microenvironment.Journal of experimental & clinical cancer research : CR · 2024Review
- Preparation and Characterization of Hydroxylated Recombinant Collagen by Incorporating Proline and Hydroxyproline in Proline-DeficientBioengineering (Basel, Switzerland) · 2024Article
- The Spatial Extracellular Proteomic Tumor Microenvironment Distinguishes Molecular Subtypes of Hepatocellular Carcinoma.Journal of proteome research · 2024Article
- ColPTMScape: An open access knowledge base for tissue-specific collagen PTM maps.Matrix biology plus · 2024Article
- Understanding the matrix: collagen modifications in tumors and their implications for immunotherapy.Journal of translational medicine · 2024Review
- The microalgaMaterials today. Bio · 2024Article
- Glycosylation Modulates the Structure and Functions of Collagen: A Review.Molecules (Basel, Switzerland) · 2024Review
- Review
- The Characterization and Cytotoxic Evaluation ofMarine drugs · 2024Article
- Characterization of early psychosis patients carrying a genetic vulnerability to redox dysregulation: a computational analysis of mechanism-based gene expression profile in fibroblasts.Molecular psychiatry · 2023Article
- Collagen Type II-Chitosan Interactions as Dependent on Hydroxylation and Acetylation Inferred from Molecular Dynamics Simulations.Molecules (Basel, Switzerland) · 2022Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Collagens are the most abundant extracellular matrix proteins in vertebrates and have a characteristic triple-helix structure. Hydroxylation of proline residues is critical for helix stability, and diminished prolyl hydroxylase activity causes wide-spread defects in connective tissues. Still, the role of proline hydroxylation in the binding of collagen receptors such as integrins is unclear. Here, we isolated skin collagen from genetically modified mice having reduced prolyl 4-hydroxylase activity. At room temperature, the reduced proline hydroxylation did not affect interactions with the recombinant integrin α2I domain, but at 37 °C, collagen hydroxylation correlated with the avidity of α2I domain binding. Of note, LC-MS/MS analysis of isolated skin collagens revealed no major changes in the hydroxyproline content of the main integrin-binding sites. Thus, the disrupted α2I domain binding at physiological temperatures was most likely due to structural destabilization of the collagenous helix. Integrin α2I binding to the triple-helical GFPGER motif was slightly weaker than to GFOGER (O = hydroxyproline). This phenomenon was more prominent when α1 integrin was tested. Integrin α1β1 expressed on CHO cells and recombinant α1I domain showed remarkably slower binding velocity and weaker avidity to GFPGER when compared with GFOGER. Structural modeling revealed the critical interaction between Arg-218 in α1I and the hydroxyproline residue in the integrin-binding motif. The role of Arg-218 was further validated by testing a variant R218D α1I domain in solid-phase binding assays. Thus, our results show that the lack of proline hydroxylation in collagen can affect integrin binding by a direct mechanism and via structural destabilization of the triple helix.
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