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8DYY

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

Summary for 8DYY
Entry DOI10.2210/pdb8dyy/pdb
EMDB information27786
DescriptorCircumsporozoite protein, 334 Fab heavy chain, 334 Fab light chain (3 entities in total)
Functional Keywordsmalaria antibody, pfcsp, immune system
Biological sourcePlasmodium falciparum
More
Total number of polymer chains19
Total formula weight461452.14
Authors
Martin, G.M.,Ward, A.B. (deposition date: 2022-08-05, release date: 2023-08-02, Last modification date: 2024-04-24)
Primary citationMartin, 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
Cited by
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
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (3.62 Å)
Structure validation

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