Cantacuzino Military-Medical Research and Development National Institute, Bucharest, Romania.
Institute of Cellular Biology and Pathology "N. Simionescu", Bucharest, Romania.
Immunogenetics. 2022 Oct;74(5):465-474. doi: 10.1007/s00251-022-01263-8. Epub 2022 May 11.
We herein analyzed all available protein-protein interfaces of the immune complexes from the Protein Data Bank whose antigens belong to pathogens or cancers that are modulated by fever in mammalian hosts. We also included, for comparison, protein interfaces from immune complexes that are not significantly modulated by the fever response. We highlight the distribution of amino acids at these viral, bacterial, protozoan and cancer epitopes, and at their corresponding paratopes that belong strictly to monoclonal antibodies. We identify the "hotspots", i.e. residues that are highly connected at such interfaces, and assess the structural, kinetic and thermodynamic parameters responsible for complex formation. We argue for an evolutionary pressure for the types of residues at these protein interfaces that may explain the role of fever as a selective force for optimizing antibody binding to antigens.
我们在此分析了来自蛋白质数据库的所有可利用的免疫复合物的蛋白质-蛋白质界面，这些免疫复合物的抗原属于在哺乳动物宿主中受发热调节的病原体或癌症。我们还包括了由发热反应没有显著调节的免疫复合物的蛋白质界面，以作比较。我们突出显示了这些病毒、细菌、原生动物和癌症抗原表位以及与其严格对应的单克隆抗体的抗体表位的氨基酸分布。我们确定了“热点”，即这些界面上高度连接的残基，并评估了负责复合物形成的结构、动力学和热力学参数。我们认为，对于这些蛋白质界面上的残基类型，可能存在一种进化压力，这种压力可以解释发热作为一种选择性力量，用于优化抗体与抗原的结合。
