6D11

Crystal structure of 1450 Fab in complex with circumsporozoite protein NANP5

Summary for 6D11

• Entry DOI: 10.2210/pdb6d11/pdb
• Related: 6D01 6D0X
• Descriptor: 1450 Antibody, Heavy chain, 1450 Antibody, Light chain, NANP5 (3 entities in total)
• Functional Keywords: malaria, antibody, circumsporozoite protein, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 5
• Total formula weight: 96829.47

Authors

Scally, S.W.,Bosch, A.,Imkeller, K.,Wardemann, H.,Julien, J.P. (deposition date: 2018-04-11, release date: 2018-06-13, Last modification date: 2018-07-04)

Primary citation

Imkeller, K.,Scally, S.W.,Bosch, A.,Marti, G.P.,Costa, G.,Triller, G.,Murugan, R.,Renna, V.,Jumaa, H.,Kremsner, P.G.,Sim, B.K.L.,Hoffman, S.L.,Mordmuller, B.,Levashina, E.A.,Julien, J.P.,Wardemann, H.
Antihomotypic affinity maturation improves human B cell responses against a repetitive epitope.
Science, 360:1358-1362, 2018

PubMed Abstract: 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 (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.

PubMed: 29880723
DOI: 10.1126/science.aar5304

Experimental method

X-RAY DIFFRACTION (3.4 Å)