Department of Ophthalmology, University of California San Francisco, School of Medicine, San Francisco, CA 941583, USA.
Department of Biochemistry, Downing Site, Cambridge CB2 1QW, UK.
Int J Mol Sci. 2023 Oct 13;24(20):15156. doi: 10.3390/ijms242015156.
Mutations in the 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.
编码内质网驻留胶原相关脯氨酸异构酶 FK506 结合蛋白 22kDa（FKBP22）的基因突变导致脊柱后侧凸型 Ehlers-Danlos 综合征（EDS），其特征是表型广泛。这种结果的一个合理解释是 FKBP22 参与了某些胶原类型的生物合成：FKBP22 选择性地结合到胶原 III、IV、VI 和 X 上，但不结合到胶原 I、II、V 和 XI 上。然而，这些结合机制从未被探索过，它们可能是 EDS 亚型异质性的基础。在这里，我们使用胶原工具箱肽文库来研究结合特异性。我们观察到 FKBP22 的结合分布在胶原螺旋上。此外，它（1）在胶原 III 上的结合比在胶原 II 肽上更高，并且（2）与正肽电荷相关。这些发现开始阐明 FKBP22 与胶原相互作用的机制。
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