Structural Features of Antibody-Peptide Recognition.
Structural Features of Antibody-Peptide Recognition.
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DOI：
10.3389/fimmu.2022.910367
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
抗体对抗原的识别是获得性免疫的关键要素。一类关键的抗体-抗原复合物由靶向蛋白质的线性表位的抗体组成，所述线性表位在某些情况下是与疫苗设计和免疫治疗相关的病毒和病原体的保守元件。在这里，我们报告了这类复合物的结构和界面特征的详细分析，基于一组近200个非冗余的高分辨率抗体-肽复合物结构，这些结构是从蛋白质数据库组装的。我们发现，抗体结合的肽采用广泛的构象，通常显示有限的二级结构，并且不同抗体结合的相同肽序列在许多情况下可以显示不同的构象。发现与抗体环接触的倾向和抗体结合构象变化的程度与与较大蛋白抗原复合物中的抗体的倾向和程度大致相似。然而，抗体-肽界面显示出比抗体-蛋白质抗原复合物更低的包埋表面积和更少的氢键，而对于抗体-肽界面，发现每个包埋界面面积的计算结合能平均更高，这可能部分是由于更大比例的包埋疏水残基和更高的形状互补性。该数据集和这些观察结果可用于未来专注于此类相互作用的研究，包括预测计算建模工作和抗体或基于表位的疫苗免疫原的设计。
Antibody recognition of antigens is a critical element of adaptive immunity. One key class of antibody-antigen complexes is comprised of antibodies targeting linear epitopes of proteins, which in some cases are conserved elements of viruses and pathogens of relevance for vaccine design and immunotherapy. Here we report a detailed analysis of the structural and interface features of this class of complexes, based on a set of nearly 200 nonredundant high resolution antibody-peptide complex structures that were assembled from the Protein Data Bank. We found that antibody-bound peptides adopt a broad range of conformations, often displaying limited secondary structure, and that the same peptide sequence bound by different antibodies can in many cases exhibit varying conformations. Propensities of contacts with antibody loops and extent of antibody binding conformational changes were found to be broadly similar to those for antibodies in complex with larger protein antigens. However, antibody-peptide interfaces showed lower buried surface areas and fewer hydrogen bonds than antibody-protein antigen complexes, while calculated binding energy per buried interface area was found to be higher on average for antibody-peptide interfaces, likely due in part to a greater proportion of buried hydrophobic residues and higher shape complementarity. This dataset and these observations can be of use for future studies focused on this class of interactions, including predictive computational modeling efforts and the design of antibodies or epitope-based vaccine immunogens.
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影响因子：
5.8
作者：
Brenke, Ryan;Hall, David R.;Kozakov, Dima
通讯作者：
Kozakov, Dima
DOI：
10.1016/j.str.2021.01.005
发表时间：
2021-06-03
期刊：
Structure (London, England : 1993)
影响因子：
--
作者：
Guest JD;Vreven T;Zhou J;Moal I;Jeliazkov JR;Gray JJ;Weng Z;Pierce BG
通讯作者：
Pierce BG
影响因子：
5.6
作者：
Honegger, A;Plückthun, A
通讯作者：
Plückthun, A
影响因子：
5.8
作者：
Dunbar, James;Deane, Charlotte M.
通讯作者：
Deane, Charlotte M.
影响因子：
8
作者：
Frappier, Vincent;Duran, Madeleine;Keating, Amy E.
通讯作者：
Keating, Amy E.