Djulbegovic Mak B, Antonietti Michael, Taylor Gonzalez David J, Mattes Robby, Kim Colin, Uversky Vladimir N, Martinez Jaime D, Karp Carol L
Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA.
Bascom Palmer Eye Institute, University of Miami, Miami, FL.
Cornea. 2025 Feb 1;44(2):234-249. doi: 10.1097/ICO.0000000000003706.
The human cornea is essential for vision, providing structural integrity and refractive power to the eye. Recent advancements have deepened our understanding of the corneal molecular composition, yet the role of intrinsically disordered proteins within the cornea is unexplored.
We analyzed 3,250 corneal proteins identified by Dyrlund et al, focusing on the epithelium, stroma, and endothelium layers. We performed a bioinformatics analysis to characterize the amino acid composition, the propensity for intrinsic protein disorder, and the distribution of protein types in 3 corneal layer proteome.
Our study demonstrates that each corneal layer exhibited unique patterns in amino acid composition related to protein disorder. Order-promoting amino acids were generally depleted except for leucine, whereas disorder-promoting amino acids like arginine and glutamic acid were enriched across all layers. Significant variations were observed in the levels of intrinsic disorder among the different corneal layers, with substantial proportions of highly disordered proteins present in each. Analysis of protein class type in each layers revealed that no significant differences were detected in the distribution of protein classifications across the layers, suggesting a consistent population of the protein types across all corneal layers.
Our findings reveal a sophisticated landscape of protein structures where intrinsic disorder varies across layers, suggesting an adaptation of the corneal proteome to the unique physiological demands of each layer. These structural variations may reflect the intricate requirements for corneal transparency, biomechanical stability, and environmental responsiveness.
人类角膜对视力至关重要,为眼睛提供结构完整性和屈光力。最近的进展加深了我们对角膜分子组成的理解,但角膜内固有无序蛋白质的作用尚未得到探索。
我们分析了Dyrlund等人鉴定的3250种角膜蛋白,重点关注上皮层、基质层和内皮层。我们进行了生物信息学分析,以表征3个角膜层蛋白质组中的氨基酸组成、蛋白质固有无序倾向和蛋白质类型分布。
我们的研究表明,每个角膜层在与蛋白质无序相关的氨基酸组成上呈现出独特的模式。除亮氨酸外,促进有序的氨基酸普遍减少,而精氨酸和谷氨酸等促进无序的氨基酸在所有层中均富集。不同角膜层之间的固有无序水平存在显著差异,每层中都存在相当比例的高度无序蛋白质。对各层蛋白质类别类型的分析表明,各层之间蛋白质分类的分布未检测到显著差异,这表明所有角膜层中的蛋白质类型群体一致。
我们的研究结果揭示了一个复杂的蛋白质结构格局,其中固有无序在各层之间有所不同,这表明角膜蛋白质组适应了各层独特的生理需求。这些结构变化可能反映了对角膜透明度、生物力学稳定性和环境响应性的复杂要求。