6WG1
Crystal structure of Fab399 in complex with NPNA6 peptide from circumsporozoite protein
Summary for 6WG1
| Entry DOI | 10.2210/pdb6wg1/pdb |
| Descriptor | Fab399 heavy chain, Fab399 light chain, NPNA6 peptide, ... (4 entities in total) |
| Functional Keywords | malaria, sporozoite, circumsporozoite protein, antibody, immune system |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 5 |
| Total formula weight | 98352.29 |
| Authors | Pholcharee, T.,Oyen, D.,Wilson, I.A. (deposition date: 2020-04-04, release date: 2020-07-29, Last modification date: 2024-10-09) |
| Primary citation | Pholcharee, T.,Oyen, D.,Flores-Garcia, Y.,Gonzalez-Paez, G.,Han, Z.,Williams, K.L.,Volkmuth, W.,Emerling, D.,Locke, E.,Richter King, C.,Zavala, F.,Wilson, I.A. Structural and biophysical correlation of anti-NANP antibodies with in vivo protection against P. falciparum. Nat Commun, 12:1063-1063, 2021 Cited by PubMed Abstract: The most advanced P. falciparum circumsporozoite protein-based malaria vaccine, RTS,S/AS01 (RTS,S), confers partial protection but with antibody titers that wane relatively rapidly, highlighting the need to elicit more potent and durable antibody responses. Here, we elucidate crystal structures, binding affinities and kinetics, and in vivo protection of eight anti-NANP antibodies derived from an RTS,S phase 2a trial and encoded by three different heavy-chain germline genes. The structures reinforce the importance of homotypic Fab-Fab interactions in protective antibodies and the overwhelmingly dominant preference for a germline-encoded aromatic residue for recognition of the NANP motif. In this study, antibody apparent affinity correlates best with protection in an in vivo mouse model, with the more potent antibodies also recognizing epitopes with repeating secondary structural motifs of type I β- and Asn pseudo 3 turns; such insights can be incorporated into design of more effective immunogens and antibodies for passive immunization. PubMed: 33594061DOI: 10.1038/s41467-021-21221-4 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.086 Å) |
Structure validation
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