探索孤儿免疫受体TREM2及其非蛋白质连接体:在体表征
Pedro Henrique Dos Santos Dantas1, Vinícius Alexandre Fiaia Costa2, Andrei Giacchetto Felice3
1Laboratory of Mucosal Immunology and Immunoinformatics, Institute of Tropical Pathology and Public Health, Federal University of Goias, Goiânia, Goiás, Brazil.
在骨髓细胞2 (TREM2) 上表达的触发受体强烈地与12个非蛋白质配体结合,特别是像心脏脂蛋白这样的脂质. 这些由特定受体区域驱动的相互作用为TREM2相关疾病提供了新的治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 结构生物学 结构生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 在骨髓细胞2 (TREM2) 上表达的触发受体是参与各种疾病的免疫受体.
- 了解TREM2与非蛋白质配体的相互作用对于治疗开发至关重要.
研究的目的:
- 为了阐明TREM2及其非蛋白质配体之间的特定相互作用.
- 为了确定潜在的药物可用部位,并指导TREM2.的药物重新定位策略.
主要方法:
- 使用了PubChem和蛋白质数据库,用于TREM2结构和连接体.
- 进行了分子对接,MM/GBSA和分子动力学模拟.
- 雇佣CavityPlus和DrugRep服务器用于药物可用部位预测和药物重新定位.
主要成果:
- TREM2对12种非蛋白质配体表现出高亲和度的结合,亲和度从-33.01 kcal/mol (酸胺) 到-80.87 kcal/mol (心脏脂蛋白).
- 在分子动力学模拟中,同位体TREM2显示出稳定的结合脂质连接物,如心血管素和酸.
- 互动主要由疏水和正电荷区域的互补性确定区域 (CDRs) 1和2进行调解,Y38-R98区域具有关键性.
结论:
- TREM2的CDR对连接体识别具有重要意义,并且代表了药物设计的有希望的目标.
- 鉴定到的相互作用和可使用药物的部位为开发针对TREM2的新疗法提供了基础.
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