8FG0

Crystal structure of the 3764 Fab in complex with the C-terminal PfCSP linker, PfCSP281-294.

8FG0 の概要

• エントリーDOI: 10.2210/pdb8fg0/pdb
• 分子名称: 3764 Fab Heavy chain, 3764 Fab Light chain, Circumsporozoite protein, ... (4 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: 6
• 化学式量合計: 99214.54

構造登録者

Burn Aschner, C.,Julien, J.P. (登録日: 2022-12-11, 公開日: 2023-05-10, 最終更新日: 2024-10-30)

主引用文献

Oludada, O.E.,Costa, G.,Burn Aschner, C.,Obraztsova, A.S.,Prieto, K.,Canetta, C.,Hoffman, S.L.,Kremsner, P.G.,Mordmuller, B.,Murugan, R.,Julien, J.P.,Levashina, E.A.,Wardemann, H.
Molecular and functional properties of human Plasmodium falciparum CSP C-terminus antibodies.
Embo Mol Med, 15:e17454-e17454, 2023

PubMed Abstract: Human monoclonal antibodies (mAbs) against the central repeat and junction domain of Plasmodium falciparum circumsporozoite protein (PfCSP) have been studied extensively to guide malaria vaccine design compared to antibodies against the PfCSP C terminus. Here, we describe the molecular characteristics and protective potential of 73 germline and mutated human mAbs against the highly immunogenic PfCSP C-terminal domain. Two mAbs recognized linear epitopes in the C-terminal linker with sequence similarity to repeat and junction motifs, whereas all others targeted conformational epitopes in the α-thrombospondin repeat (α-TSR) domain. Specificity for the polymorphic Th2R/Th3R but not the conserved RII+/CS.T3 region in the α-TSR was associated with IGHV3-21/IGVL3-21 or IGLV3-1 gene usage. Although the C terminus specific mAbs showed signs of more efficient affinity maturation and class-switching compared to anti-repeat mAbs, live sporozoite binding and inhibitory activity was limited to a single C-linker reactive mAb with cross-reactivity to the central repeat and junction. The data provide novel insights in the human anti-C-linker and anti-α-TSR antibody response that support exclusion of the PfCSP C terminus from malaria vaccine designs.

PubMed: 37082831
DOI: 10.15252/emmm.202317454

実験手法

X-RAY DIFFRACTION (2.36 Å)