6d0x

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Crystal structure of chimeric H.2140 / K.1210 Fab in complex with circumsporozoite protein NANP3Crystal structure of chimeric H.2140 / K.1210 Fab in complex with circumsporozoite protein NANP3

Structural highlights

6d0x 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 1.849Å
Ligands:,
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

Affinity maturation selects B cells expressing somatically mutated antibody variants with improved antigen-binding properties to protect from invading pathogens. We determined the molecular mechanism underlying the clonal selection and affinity maturation of human B cells expressing protective antibodies against the circumsporozoite protein of the malaria parasite Plasmodium falciparum (PfCSP). We show in molecular detail that the repetitive nature of PfCSP facilitates direct homotypic interactions between two PfCSP repeat-bound monoclonal antibodies, thereby improving antigen affinity and B cell activation. These data provide a mechanistic explanation for the strong selection of somatic mutations that mediate homotypic antibody interactions after repeated parasite exposure in humans. Our findings demonstrate a different mode of antigen-mediated affinity maturation to improve antibody responses to PfCSP and presumably other repetitive antigens.

Antihomotypic affinity maturation improves human B cell responses against a repetitive epitope.,Imkeller K, Scally SW, Bosch A, Marti GP, Costa G, Triller G, Murugan R, Renna V, Jumaa H, Kremsner PG, Sim BKL, Hoffman SL, Mordmuller B, Levashina E, Julien JP, Wardemann H Science. 2018 Jun 7. pii: science.aar5304. doi: 10.1126/science.aar5304. PMID:29880723[1]

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

See Also

References

  1. Imkeller K, Scally SW, Bosch A, Marti GP, Costa G, Triller G, Murugan R, Renna V, Jumaa H, Kremsner PG, Sim BKL, Hoffman SL, Mordmuller B, Levashina E, Julien JP, Wardemann H. Antihomotypic affinity maturation improves human B cell responses against a repetitive epitope. Science. 2018 Jun 7. pii: science.aar5304. doi: 10.1126/science.aar5304. PMID:29880723 doi:http://dx.doi.org/10.1126/science.aar5304

6d0x, resolution 1.85Å

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