6uc5
Fab397 in complex with NPNA peptide
Structural highlights
FunctionPublication Abstract from PubMedMalaria vaccine candidate RTS,S/AS01 is based on the central and C-terminal regions of the circumsporozoite protein (CSP) of P. falciparum. mAb397 was isolated from a volunteer in an RTS,S/AS01 clinical trial, and it protects mice from infection by malaria sporozoites. However, mAb397 originates from the less commonly used VH3-15 germline gene compared to the VH3-30/33 antibodies generally elicited by RTS,S to the central NANP repeat region of CSP. The crystal structure of mAb397 with an NPNA4 peptide shows that the central NPNA forms a type I beta-turn and is the main recognition motif. In most anti-NANP antibodies studied to date, a germline-encoded Trp is used to engage the Pro in NPNA beta-turns, but here the Trp interacts with the first Asn. This "conserved" Trp, however, can arise from different germline genes and be located in the heavy or the light chain. Variation in the terminal psi angles of the NPNA beta-turns results in different dispositions of the subsequent NPNA and, hence, different stoichiometries and modes of antibody binding to rsCSP. Diverse protective antibodies against NANP repeats are therefore not limited to a single germline gene response or mode of binding. Diverse Antibody Responses to Conserved Structural Motifs in Plasmodium falciparum Circumsporozoite Protein.,Pholcharee T, Oyen D, Torres JL, Flores-Garcia Y, Martin GM, Gonzalez-Paez GE, Emerling D, Volkmuth W, Locke E, King CR, Zavala F, Ward AB, Wilson IA J Mol Biol. 2020 Feb 14;432(4):1048-1063. doi: 10.1016/j.jmb.2019.12.029. Epub, 2019 Dec 27. PMID:31883801[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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