6PBV

Crystal structure of Fab668 complex

6PBV の概要

• エントリーDOI: 10.2210/pdb6pbv/pdb
• 分子名称: Fab668 light chain, Fab668 heavy chain, Junctional peptide, ... (5 entities in total)
• 機能のキーワード: fab fragment, immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 97710.53

構造登録者

Oyen, D.,Wilson, I.A. (登録日: 2019-06-14, 公開日: 2020-03-04, 最終更新日: 2024-10-23)

主引用文献

Oyen, D.,Torres, J.L.,Aoto, P.C.,Flores-Garcia, Y.,Binter, S.,Pholcharee, T.,Carroll, S.,Reponen, S.,Wash, R.,Liang, Q.,Lemiale, F.,Locke, E.,Bradley, A.,King, C.R.,Emerling, D.,Kellam, P.,Zavala, F.,Ward, A.B.,Wilson, I.A.
Structure and mechanism of monoclonal antibody binding to the junctional epitope of Plasmodium falciparum circumsporozoite protein.
Plos Pathog., 16:e1008373-e1008373, 2020

PubMed Abstract: Lasting protection has long been a goal for malaria vaccines. The major surface antigen on Plasmodium falciparum sporozoites, the circumsporozoite protein (PfCSP), has been an attractive target for vaccine development and most protective antibodies studied to date interact with the central NANP repeat region of PfCSP. However, it remains unclear what structural and functional characteristics correlate with better protection by one antibody over another. Binding to the junctional region between the N-terminal domain and central NANP repeats has been proposed to result in superior protection: this region initiates with the only NPDP sequence followed immediately by NANP. Here, we isolated antibodies in Kymab mice immunized with full-length recombinant PfCSP and two protective antibodies were selected for further study with reactivity against the junctional region. X-ray and EM structures of two monoclonal antibodies, mAb667 and mAb668, shed light on their differential affinity and specificity for the junctional region. Importantly, these antibodies also bind to the NANP repeat region with equal or better affinity. A comparison with an NANP-only binding antibody (mAb317) revealed roughly similar but statistically distinct levels of protection against sporozoite challenge in mouse liver burden models, suggesting that junctional antibody protection might relate to the ability to also cross-react with the NANP repeat region. Our findings indicate that additional efforts are necessary to isolate a true junctional antibody with no or much reduced affinity to the NANP region to elucidate the role of the junctional epitope in protection.

PubMed: 32150583
DOI: 10.1371/journal.ppat.1008373

実験手法

X-RAY DIFFRACTION (1.566 Å)