7RQP

Structure of PfCSP NPNV binding antibody L9

7RQP の概要

• エントリーDOI: 10.2210/pdb7rqp/pdb
• 分子名称: L9 Heavy Chain, L9 Kappa Chain (3 entities in total)
• 機能のキーワード: malaria, antibody, immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 48072.69

構造登録者

Hurlburt, N.K.,Pancera, M. (登録日: 2021-08-06, 公開日: 2022-03-02, 最終更新日: 2024-11-13)

主引用文献

Wang, L.T.,Hurlburt, N.K.,Schon, A.,Flynn, B.J.,Flores-Garcia, Y.,Pereira, L.S.,Kiyuka, P.K.,Dillon, M.,Bonilla, B.,Zavala, F.,Idris, A.H.,Francica, J.R.,Pancera, M.,Seder, R.A.
The light chain of the L9 antibody is critical for binding circumsporozoite protein minor repeats and preventing malaria.
Cell Rep, 38:110367-110367, 2022

PubMed Abstract: L9 is a potent human monoclonal antibody (mAb) that preferentially binds two adjacent NVDP minor repeats and cross-reacts with NANP major repeats of the Plasmodium falciparum circumsporozoite protein (PfCSP) on malaria-infective sporozoites. Understanding this mAb's ontogeny and mechanisms of binding PfCSP will facilitate vaccine development. Here, we isolate mAbs clonally related to L9 and show that this B cell lineage has baseline NVDP affinity and evolves to acquire NANP reactivity. Pairing the L9 kappa light chain (L9κ) with clonally related heavy chains results in chimeric mAbs that cross-link two NVDPs, cross-react with NANP, and more potently neutralize sporozoites in vivo compared with their original light chain. Structural analyses reveal that the chimeric mAbs bound minor repeats in a type-1 β-turn seen in other repeat-specific antibodies. These data highlight the importance of L9κ in binding NVDP on PfCSP to neutralize sporozoites and suggest that PfCSP-based immunogens might be improved by presenting ≥2 NVDPs.

PubMed: 35172158
DOI: 10.1016/j.celrep.2022.110367

実験手法

X-RAY DIFFRACTION (2.98 Å)