Abstract
Purpose :
Our objective was to analyze the human vitreous humor proteome, focusing on the identification characterization of intrinsically disordered proteins (IDPs). IDPs, known for lacking a stable three-dimensional structure, retain significant biological functionality. A key aspect of our study was to investigate the propensity of these IDPs for Liquid-Liquid Phase Separation (LLPS), a process critical in cellular organization and function. By exploring the relationship between IDPs and LLPS, we aim to deepen our understanding of their roles in the vitreous humor proteome, providing insights into the molecular behavior of this ocular fluid.
Methods :
We examined a set of 1,240 vitreous proteins previously identified in published research. The amino acid sequences of the proteins were analyzed using various computational tools including the Phase Separation Predictor (PSPredictor) and the Predictor of Natural Disordered Regions Version 2 (PONDR).
Results :
In our analysis using PONDR, we predicted 334 proteins (26.9%) as highly disordered, 852 proteins (68.8%) as moderate disorder or conformational flexibility, and only 54 proteins (4.3%) as highly structured and ordered. Additionally, our analysis predicts that 308 proteins (24.84%) are likely to undergo Liquid-Liquid Phase Separation (LLPS).
Conclusions :
Our study suggests the presence of intrinsic disorder and LLPS propensities in the vitreous proteome. These findings highlight the complex molecular landscape of the vitreous but also suggest broader implications for its global structure. For instance, the phenomenon of vitreous syneresis, which involves a degree of phase separation, could potentially be linked to the dynamics of LLPS and intrinsic protein disorder. We speculate that alterations in ocular or systemic health might impact these properties, thereby affecting the overall structure and functionality of the vitreous.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.