7F8I

Crystal structure of HPV6 L1 pentamer

これはPDB形式変換不可エントリーです。

7F8I の概要

• エントリーDOI: 10.2210/pdb7f8i/pdb
• 分子名称: Major capsid protein L1 (1 entity in total)
• 機能のキーワード: viral protein
• 由来する生物種: Human papillomavirus type 6
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 550981.13

構造登録者

Wang, Z.P.,Wang, D.N.,Gu, Y.,Li, S.W. (登録日: 2021-07-02, 公開日: 2022-07-06, 最終更新日: 2025-02-26)

主引用文献

Wang, Z.,Wang, D.,Chen, J.,Gao, F.,Jiang, Y.,Yang, C.,Qian, C.,Chi, X.,Zhang, S.,Xu, Y.,Lu, Y.,Shen, J.,Zhang, C.,Li, J.,Zhou, L.,Li, T.,Zheng, Q.,Yu, H.,Li, S.,Xia, N.,Gu, Y.
Rational design of a cross-type HPV vaccine through immunodominance shift guided by a cross-neutralizing antibody.
Sci Bull (Beijing), 69:512-525, 2024

PubMed Abstract: In vaccine development, broadly or cross-type neutralizing antibodies (bnAbs or cnAbs) are frequently targeted to enhance protection. Utilizing immunodominant antibodies could help fine-tune vaccine immunogenicity and augment the precision of immunization strategies. However, the methodologies to capitalize on the attributes of bnAbs in vaccine design have not been clearly elucidated. In this study, we discovered a cross-type neutralizing monoclonal antibody, 13H5, against human papillomavirus 6 (HPV6) and HPV11. This nAb exhibited a marked preference for HPV6, demonstrating superior binding activity to virus-like particles (VLPs) and significantly higher prevalence in anti-HPV6 human serum as compared to HPV11 antiserum (90% vs. 31%). Through co-crystal structural analysis of the HPV6 L1 pentamer:13H5 complex, we delineated the epitope as spanning four segments of amino acids (Phe42-Ala47, Gly172-Asp173, Glu255-Val275, and Val337-Tyr351) on the L1 surface loops. Further interaction analysis and site-directed mutagenesis revealed that the Ser341 residue in the HPV6 HI loop plays a critical role in the interaction between 13H5 and L1. Substituting Ser341 with alanine, which is the residue type present in HPV11 L1, almost completely abolished binding activity to 13H5. By swapping amino acids in the HPV11 HI loop with corresponding residues in HPV6 L1 (Ser341, Thr338, and Thr339), we engineered chimeric HPV11-6HI VLPs. Remarkably, the chimeric HPV11-6HI VLPs shifted the high immunodominance of 13H5 from HPV6 to the engineered VLPs and yielded comparable neutralization titers for both HPV6 and HPV11 in mice and non-human primates. This approach paves the way for the design of broadly protective vaccines from antibodies within the main immunization reservoir.

PubMed: 38160175
DOI: 10.1016/j.scib.2023.12.021

実験手法

X-RAY DIFFRACTION (3.366 Å)