6wfx

Crystal structure of Fab395 in complex with NPNA2 peptide from circumsporozoite protein

spinqualitylabelsall models 6wfx, resolution 2.59Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6wfx is a 3 chain structure with sequence from Homo sapiens and Plasmodium falciparum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.59Å Ligands: ACE, NH2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CSP_PLAFA The circumsporozoite protein is the immunodominant surface antigen on the sporozoite (the infective stage of the malaria parasite that is transmitted from the mosquito to the vertebrate host). Publication Abstract from PubMed 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 beta- and Asn pseudo 3(10) turns; such insights can be incorporated into design of more effective immunogens and antibodies for passive immunization. Structural and biophysical correlation of anti-NANP antibodies with in vivo protection against P. falciparum.,Pholcharee T, Oyen D, Flores-Garcia Y, Gonzalez-Paez G, Han Z, Williams KL, Volkmuth W, Emerling D, Locke E, Richter King C, Zavala F, Wilson IA Nat Commun. 2021 Feb 16;12(1):1063. doi: 10.1038/s41467-021-21221-4. PMID:33594061 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Monoclonal Antibodies 3D structures

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