8DYY

Cryo-EM structure of 334 Fab in complex with recombinant shortened Plasmodium falciparum circumsporozoite protein (rsCSP)

8DYY の概要

• エントリーDOI: 10.2210/pdb8dyy/pdb
• EMDBエントリー: 27786
• 分子名称: Circumsporozoite protein, 334 Fab heavy chain, 334 Fab light chain (3 entities in total)
• 機能のキーワード: malaria antibody, pfcsp, immune system
• 由来する生物種: Plasmodium falciparum; 詳細
• タンパク質・核酸の鎖数: 19
• 化学式量合計: 461452.14

構造登録者

Martin, G.M.,Ward, A.B. (登録日: 2022-08-05, 公開日: 2023-08-02, 最終更新日: 2025-05-28)

主引用文献

Martin, G.M.,Torres, J.L.,Pholcharee, T.,Oyen, D.,Flores-Garcia, Y.,Gibson, G.,Moskovitz, R.,Beutler, N.,Jung, D.D.,Copps, J.,Lee, W.H.,Gonzalez-Paez, G.,Emerling, D.,MacGill, R.S.,Locke, E.,King, C.R.,Zavala, F.,Wilson, I.A.,Ward, A.B.
Affinity-matured homotypic interactions induce spectrum of PfCSP structures that influence protection from malaria infection.
Nat Commun, 14:4546-4546, 2023

PubMed Abstract: The generation of high-quality antibody responses to Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP), the primary surface antigen of Pf sporozoites, is paramount to the development of an effective malaria vaccine. Here we present an in-depth structural and functional analysis of a panel of potent antibodies encoded by the immunoglobulin heavy chain variable (IGHV) gene IGHV3-33, which is among the most prevalent and potent antibody families induced in the anti-PfCSP immune response and targets the Asn-Ala-Asn-Pro (NANP) repeat region. Cryo-electron microscopy (cryo-EM) reveals a remarkable spectrum of helical antibody-PfCSP structures stabilized by homotypic interactions between tightly packed fragments antigen binding (Fabs), many of which correlate with somatic hypermutation. We demonstrate a key role of these mutated homotypic contacts for high avidity binding to PfCSP and in protection from Pf malaria infection. Together, these data emphasize the importance of anti-homotypic affinity maturation in the frequent selection of IGHV3-33 antibodies and highlight key features underlying the potent protection of this antibody family.

PubMed: 37507365
DOI: 10.1038/s41467-023-40151-x

実験手法

ELECTRON MICROSCOPY (3.62 Å)