Abreu Velez Ana Maria, Ramírez-Posada Mariana, Howard Michael S
Georgia Dermatopathology Associates, Atlanta, Georgia, USA.
Dermatologic Epidemiology Postdoctoral Fellow, Stanford University Medical Center, Palo Alto, California, USA.
Dermatol Pract Concept. 2025 Jul 31;15(3):5097. doi: 10.5826/dpc.1503a5097.
A new variant of endemic pemphigus foliaceus, El Bagre-EPF, is an orphan autoimmune disease occurring in El Bagre and neighboring municipalities in Colombia, South America.
We aimed to evaluate current state-of-the-art databases and protein-protein interactomes, focusing on post-translational modifications as potential tools to study interactions among El Bagre-EPF antigen proteins.
We consulted multiple databases for the known target antigens and their protein-protein interactions. We searched for their network nodes (they represent proteins; each node corresponded to all the proteins produced by a single, protein-coding gene locus). We also searched for any post-translational modifications.
We identified similarities in proteins bound by several autoantigens but also found differences in protein linkages. We found that desmoglein, periplakin, desmoplakins, and proteins from subfamilies of the Armadillo repeat proteins and some spectrin domains linked to other cell junctions; these played important roles in membrane-plaque and intermediate filament junctions. A typical drawback in current databases is the lack of information on lipid-protein interactions.
Our results show that state-of-the-art protein databases as tools for studies of interactomes fall short in areas including tertiary and quaternary protein interactions and in vivo protein functioning. Enhanced three-dimensional or multi-dimensional functions are required for more accurate interactome analyses.
地方性落叶型天疱疮的一种新变体,即埃尔巴格雷 - 地方性落叶型天疱疮(El Bagre-EPF),是一种发生在南美洲哥伦比亚埃尔巴格雷及周边市镇的罕见自身免疫性疾病。
我们旨在评估当前最先进的数据库和蛋白质 - 蛋白质相互作用组,重点关注翻译后修饰,将其作为研究埃尔巴格雷 - 地方性落叶型天疱疮抗原蛋白之间相互作用的潜在工具。
我们查阅了多个数据库,以获取已知的靶抗原及其蛋白质 - 蛋白质相互作用信息。我们搜索了它们的网络节点(它们代表蛋白质;每个节点对应于由单个蛋白质编码基因位点产生的所有蛋白质)。我们还搜索了任何翻译后修饰。
我们发现几种自身抗原结合的蛋白质存在相似性,但也发现了蛋白质连接方式的差异。我们发现桥粒芯糖蛋白、周膜蛋白、桥粒斑蛋白以及来自犰狳重复蛋白亚家族和一些与其他细胞连接相关的血影蛋白结构域的蛋白质;这些在膜斑和中间丝连接中发挥着重要作用。当前数据库的一个典型缺陷是缺乏关于脂 - 蛋白相互作用的信息。
我们的结果表明,作为研究相互作用组的工具,当前最先进的蛋白质数据库在包括蛋白质三级和四级相互作用以及体内蛋白质功能等方面存在不足。需要增强三维或多维功能才能进行更准确的相互作用组分析。