7RQP

Structure of PfCSP NPNV binding antibody L9

Summary for 7RQP

• Entry DOI: 10.2210/pdb7rqp/pdb
• Descriptor: L9 Heavy Chain, L9 Kappa Chain (3 entities in total)
• Functional Keywords: malaria, antibody, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 2
• Total formula weight: 48072.69

Authors

Hurlburt, N.K.,Pancera, M. (deposition date: 2021-08-06, release date: 2022-03-02, Last modification date: 2024-11-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.98 Å)