8EKF
X-ray crystal structure of 311R Fab in complex with the PfCSP peptide NPNA-3
This is a non-PDB format compatible entry.
Summary for 8EKF
| Entry DOI | 10.2210/pdb8ekf/pdb |
| Related | 6AXK |
| Descriptor | 311R Heavy Chain, 311R Light Chain, PfCSP peptide NPNA-3, ... (4 entities in total) |
| Functional Keywords | antibody, antigen, malaria, immune system |
| Biological source | Homo sapiens More |
| Total number of polymer chains | 3 |
| Total formula weight | 47974.31 |
| Authors | Moskovitz, R.,Wilson, I.A. (deposition date: 2022-09-20, release date: 2022-10-19, Last modification date: 2024-10-30) |
| Primary citation | 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 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: 37507365DOI: 10.1038/s41467-023-40151-x PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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