ArticleProceedings of the National Academy of Sciences of the United States of America2016
Disentangling mechanisms involved in collagen pyridinoline cross-linking: The immunophilin FKBP65 is critical for dimerization of lysyl hydroxylase 2.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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49 citing papers in PubMed, 84 citations in OpenAlex.
- Collagen in Fibrotic Diseases.Sub-cellular biochemistry · 2026Review
- Molecular drivers of osteogenesis imperfecta: a cellular and extracellular collagen disease.Clinical science (London, England : 1979) · 2025Review
- Collagen IV biosynthesis: Intracellular choreography of post-translational modifications.Matrix biology : journal of the International Society for Matrix Biology · 2025Review
- FKBP10 expression and TP53 mutation predict prognosis and chemotherapy response in triple-negative breast cancer.Discover oncology · 2025Article
- The structural basis for the human procollagen lysine hydroxylation and dual-glycosylation.Nature communications · 2025Article
- Loss of the long form of Plod2 phenocopies contractures of Bruck syndrome-osteogenesis imperfecta.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024Article
- Generation of bone-specific lysyl hydroxylase 2 knockout mice and their phenotypes.Biochemistry and biophysics reports · 2024Article
- DDX5 inhibits hyaline cartilage fibrosis and degradation in osteoarthritis via alternative splicing and G-quadruplex unwinding.Nature aging · 2024Article
- A novel compound heterozygous variation in theHeliyon · 2024Article
- The integration of bulk and single-cell sequencing data revealed the function of FKBP10 in the gastric cancer microenvironment.Translational cancer research · 2024Article
- Knockdown of Hyaluronan synthase 2 suppresses liver fibrosis in mice via induction of transcriptomic changes similar to 4MU treatment.Scientific reports · 2024Article
- FKBP10 promotes clear cell renal cell carcinoma progression and regulates sensitivity to the HIF2α blockade by facilitating LDHA phosphorylation.Cell death & disease · 2024Article
- Emerging Landscape of Osteogenesis Imperfecta Pathogenesis and Therapeutic Approaches.ACS pharmacology & translational science · 2024Review
- Procollagen-lysine 2-oxoglutarate 5-dioxygenases are responsible for 5R-hydroxylysine modification of therapeutic T-cell bispecific monoclonal antibodies produced by Chinese hamster ovary cells.Frontiers in bioengineering and biotechnology · 2024Article
- Biophysical interplay between extracellular matrix remodeling and hypoxia signaling in regulating cancer metastasis.Frontiers in cell and developmental biology · 2024Review
- Features of Congenital Arthrogryposis Due to Abnormalities in Collagen Homeostasis, a Scoping Review.International journal of molecular sciences · 2023Article
- Identification of FKBP10 prognostic value in lung adenocarcinoma patients with surgical resection of brain metastases: A retrospective single-institution cohort study.Clinics (Sao Paulo, Brazil) · 2023Article
- Superenhancer drives a tumor-specific splicing variant of MARCO to promote triple-negative breast cancer progression.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Lysyl hydroxylase 2 mediated collagen post-translational modifications and functional outcomes.Scientific reports · 2022Article
- Metaphyseal and posterior rib fractures in osteogenesis imperfecta: Case report and review of the literature.Bone reports · 2022Article
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4 authors at 2 institutions in 1 country.
Funding
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Abstract
Collagens are subjected to extensive posttranslational modifications, such as lysine hydroxylation. Bruck syndrome (BS) is a connective tissue disorder characterized at the molecular level by a loss of telopeptide lysine hydroxylation, resulting in reduced collagen pyridinoline cross-linking. BS results from mutations in the genes coding for lysyl hydroxylase (LH) 2 or peptidyl-prolyl cis-trans isomerase (PPIase) FKBP65. Given that the immunophilin FKBP65 does not exhibit LH activity, it is likely that LH2 activity is somehow dependent on FKPB65. In this report, we provide insights regarding the interplay between LH2 and FKBP65. We found that FKBP65 forms complexes with LH2 splice variants LH2A and LH2B but not with LH1 and LH3. Ablating the catalytic activity of FKBP65 or LH2 did not affect complex formation. Both depletion of FKBP65 and inhibition of FKBP65 PPIase activity reduced the dimeric (active) form of LH2 but did not affect the binding of monomeric (inactive) LH2 to procollagen Iα1. Furthermore, we show that LH2A and LH2B cannot form heterodimers with each other but are able to form heterodimers with LH1 and LH3. Collectively, our results indicate that FKBP65 is linked to pyridinoline cross-linking by specifically mediating the dimerization of LH2. Moreover, FKBP65 does not interact with LH1 and LH3, explaining why in BS triple-helical hydroxylysines are not affected. Our results provide a mechanistic link between FKBP65 and the loss of pyridinolines and may hold the key to future treatments for diseases related to collagen cross-linking anomalies, such as fibrosis and cancer.
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