8eh5

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Cryo-EM structure of L9 Fab in complex with rsCSP

Structural highlights

8eh5 is a 7 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:	Electron Microscopy, Resolution 3.36Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

A0A5Q0MU09_PLAFA Essential sporozoite protein. In the mosquito vector, required for sporozoite development in the oocyst, migration through the vector hemolymph and entry into the vector salivary glands. In the vertebrate host, required for sporozoite migration through the host dermis and infection of host hepatocytes. Binds to highly sulfated heparan sulfate proteoglycans (HSPGs) on the surface of host hepatocytes.[RuleBase:RU369056] In the vertebrate host, binds to highly sulfated heparan sulfate proteoglycans (HSPGs) on the surface of host hepatocytes and is required for sporozoite invasion of the host hepatocytes.[RuleBase:RU369056]

Publication Abstract from PubMed

A primary objective in malaria vaccine design is the generation of high-quality antibody responses against the circumsporozoite protein of the malaria parasite, Plasmodium falciparum (PfCSP). To enable rational antigen design, we solved a cryo-EM structure of the highly potent anti-PfCSP antibody L9 in complex with recombinant PfCSP. We found that L9 Fab binds multivalently to the minor (NPNV) repeat domain, which is stabilized by a unique set of affinity-matured homotypic, antibody-antibody contacts. Molecular dynamics simulations revealed a critical role of the L9 light chain in integrity of the homotypic interface, which likely impacts PfCSP affinity and protective efficacy. These findings reveal the molecular mechanism of the unique NPNV selectivity of L9 and emphasize the importance of anti-homotypic affinity maturation in protective immunity against P. falciparum.

Structural basis of epitope selectivity and potent protection from malaria by PfCSP antibody L9.,Martin GM, Fernandez-Quintero ML, Lee WH, Pholcharee T, Eshun-Wilson L, Liedl KR, Pancera M, Seder RA, Wilson IA, Ward AB Nat Commun. 2023 May 17;14(1):2815. doi: 10.1038/s41467-023-38509-2. PMID:37198165^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Martin GM, Fernández-Quintero ML, Lee WH, Pholcharee T, Eshun-Wilson L, Liedl KR, Pancera M, Seder RA, Wilson IA, Ward AB. Structural basis of epitope selectivity and potent protection from malaria by PfCSP antibody L9. Nat Commun. 2023 May 17;14(1):2815. PMID:37198165 doi:10.1038/s41467-023-38509-2