蛋白质组学与生物信息学在创伤性脑损伤生物标志物发现中的结合。

Biotechnologia Pub Date : 2025-06-30 eCollection Date: 2025-01-01 DOI:10.5114/bta/202470
Mohamed M Mohamed, El-Sayed A El-Absawy, Hala M Ahmed, Mohamed E Hasan
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引用次数: 0

摘要

背景:创伤性脑损伤(TBI)是一个重大的医学危机,没有fda批准的治疗方法来改善功能结局。关键的生物标志物,如胶质纤维酸性蛋白(GFAP)、S-100钙结合蛋白B (S-100B)和泛素c端水解酶L1 (UCH-L1),对理解脑外伤病理至关重要。材料和方法:本研究结合蛋白质组学和生物信息学方法,探索已建立的TBI生物标志物GFAP、S-100B和UCH-L1的结构和功能复杂性。结果:我们利用PredictProtein进行的综合二级结构和溶剂可及性评估证实了GFAP和S-100B中α -螺旋的优势,而ch - l1则显示了螺旋(65.00、67.39和40.81%)、β链(6.20、0和17.94%)和线圈(40.81、17.94和41.26%)的平衡混合。基于均方根偏差(RMSD)、TM-score和C-score评估,AlphaFold和I-TASSER被认为是预测三种靶蛋白全长三级结构的最佳服务器。蛋白质基序数据库扫描分别预测了GFAP、S-100B和UCH-L1的4个、8个和1个蛋白质结合基序和2个、3个和1个翻译后修饰。结论:GFAP在轴突转运和突触可塑性中的作用通过灯丝和DUF1664等基序得到强调。S-100/ icabp型钙结合结构域支持S-100B与脑损伤后神经炎症和氧化应激的关联。UCH-L1对TBI的双重影响被Peptidase_C12基序进一步阐明。这种方法加深了我们对这些生物标志物的理解,为TBI的靶向诊断铺平了道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Integration of proteomics and bioinformatics in traumatic brain injury biomarker discovery.

Background: Traumatic brain injury (TBI) is a significant medical crisis with no FDA-approved therapies to improve functional outcomes. Key biomarkers, such as glial fibrillary acidic protein (GFAP), S-100 calcium-binding protein B (S-100B), and ubiquitin C-terminal hydrolase L1 (UCH-L1), are crucial for understanding TBI pathology.

Materials and methods: This study integrates proteomic and bioinformatic approaches to explore established TBI biomarkers' structural and functional complexities: GFAP, S-100B, and UCH-L1.

Results: Our comprehensive secondary structure and solvent accessibility assessment, conducted with PredictProtein, confirmed the predominance of alpha-helices in GFAP and S-100B, while UCH-L1 displayed a balanced mix of helices (65.00, 67.39, and 40.81%), beta strands (6.20, 0, and 17.94%), and coils (40.81, 17.94, and 41.26%). AlphaFold and I-TASSER were identified as the best servers for full-length tertiary structure prediction for the three target proteins, based on root-mean-square deviation (RMSD), TM-score, and C-score assessments. Protein motif database scans predicted four, eight, and one protein-binding motifs and two, three, and one post-translational modifications for GFAP, S-100B, and UCH-L1, respectively.

Conclusions: GFAP's role in axonal transport and synaptic plasticity was emphasized through motifs such as Filament and DUF1664. S-100B's association with neuroinflammation and oxidative stress post-TBI was supported by the S-100/ICaBP-type calcium-binding domain. UCH-L1's dualistic impact on TBI was further clarified by the Peptidase_C12 motif. This approach deepens our comprehension of these biomarkers and paves the way for targeted diagnostics in TBI.

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