Local Net Charge State of Collagen Triple Helix Is a Determinant of FKBP22 Binding to Collagen III

Int J Mol Sci. 2023 Oct 13;24(20):15156. doi: 10.3390/ijms242015156.


Mutations in the FKBP14 gene encoding the endoplasmic reticulum resident collagen-related proline isomerase FK506 binding protein 22 kDa (FKBP22) result in kyphoscoliotic Ehlers-Danlos Syndrome (EDS), which is characterized by a broad phenotypic outcome. A plausible explanation for this outcome is that FKBP22 participates in the biosynthesis of subsets of collagen types: FKBP22 selectively binds to collagens III, IV, VI, and X, but not to collagens I, II, V, and XI. However, these binding mechanisms have never been explored, and they may underpin EDS subtype heterogeneity. Here, we used collagen Toolkit peptide libraries to investigate binding specificity. We observed that FKBP22 binding was distributed along the collagen helix. Further, it (1) was higher on collagen III than collagen II peptides and it (2) was correlated with a positive peptide charge. These findings begin to elucidate the mechanism by which FKBP22 interacts with collagen.

Keywords: Ehlers–Danlos Syndrome; collagen Toolkit; endoplasmic reticulum; extracellular matrix; triple-helical peptides.

MeSH terms

  • Collagen / genetics
  • Ehlers-Danlos Syndrome* / genetics
  • Humans
  • Mutation
  • Peptidylprolyl Isomerase / genetics
  • Tacrolimus Binding Proteins* / metabolism


  • FKBP22
  • Tacrolimus Binding Proteins
  • Collagen
  • Peptidylprolyl Isomerase
  • FKBP14 protein, human