Understanding the Molecular Determinants Driving the Immunological Specificity of the Protective Pilus 2a Backbone Protein of Group B Streptococcus
Understanding the Molecular Determinants Driving the Immunological Specificity of the Protective Pilus 2a Backbone Protein of Group B Streptococcus
复制标题
了解驱动 B 族链球菌保护性菌毛 2a 骨架蛋白免疫特异性的分子决定因素
DOI：
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Sergei L. Kosakovsky
中科院分区：
文献类型：
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作者：
A. Nuccitelli;D. Rinaudo;B. Brogioni;R. Cozzi;M. Ferrer;Daniel Yero;J. Telford;G. Grandi;X. Daura;M. Zacharias;D. Maione;Sergei L. Kosakovsky
菌毛2a主干蛋白(BP-2a)是潜在的B群链球菌疫苗配方中最具结构和功能特征的成分之一。它的特点是有六个主要的免疫学上不同的等位基因变异，每个变异都能诱导变异特异性保护。为了研究驱动BP-2a变异免疫原性的分子决定因素，根据单个残基的贡献，我们根据识别细菌表面聚合菌毛结构的能力制备了六种针对特定蛋白质变体的单抗。三种单抗还能够诱导补体依赖的吞噬细胞对活的GBS的杀伤作用，并靶向存在于蛋白质结构定义和免疫优势结构域D3中的相同线性表位。模拟的单链抗体序列与BP-2a晶体结构之间的分子对接揭示了一些非保守的抗原残基在结合界面上的潜在作用。突变分析证实，为了获得mAbs与蛋白质抗原的特异性结合，需要在结合界面上的电荷、大小和极性之间取得完美的平衡，以进行中和反应。
The pilus 2a backbone protein (BP-2a) is one of the most structurally and functionally characterized components of a potential vaccine formulation against Group B Streptococcus. It is characterized by six main immunologically distinct allelic variants, each inducing variant-specific protection. To investigate the molecular determinants driving the variant immunogenic specificity of BP-2a, in terms of single residue contributions, we generated six monoclonal antibodies against a specific protein variant based on their capability to recognize the polymerized pili structure on the bacterial surface. Three mAbs were also able to induce complement-dependent opsonophagocytosis killing of live GBS and target the same linear epitope present in the structurally defined and immunodominant domain D3 of the protein. Molecular docking between the modelled scFv antibody sequences and the BP-2a crystal structure revealed the potential role at the binding interface of some non-conserved antigen residues. Mutagenesis analysis confirmed the necessity of a perfect balance between charges, size and polarity at the binding interface to obtain specific binding of mAbs to the protein antigen for a neutralizing response.
影响因子：
4.4
作者：
E. Kabat;Te Wu Tai Te Wu-Te-Wu-Tai-Te-Wu-2244585577
通讯作者：
E. Kabat;Te Wu Tai Te Wu-Te-Wu-Tai-Te-Wu-2244585577
影响因子：
10.7
作者：
Pond, SLK;Frost, SDW
通讯作者：
Frost, SDW
影响因子：
7.4
作者：
Peter, JF;Tomer, KB
通讯作者：
Tomer, KB