5SZF

2A10 FAB fragment 2.54 Angstoms

Summary for 5SZF

• Entry DOI: 10.2210/pdb5szf/pdb
• Descriptor: 2A10 antibody FAB fragment light chain, 2A10 antibody FAB fragment heavy chain, SULFATE ION, ... (4 entities in total)
• Functional Keywords: malaria antibody, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 2
• Total formula weight: 47535.58

Authors

Jackson, C.J.,Fisher, C. (deposition date: 2016-08-13, release date: 2017-07-26, Last modification date: 2024-10-16)

Primary citation

Fisher, C.R.,Sutton, H.J.,Kaczmarski, J.A.,McNamara, H.A.,Clifton, B.,Mitchell, J.,Cai, Y.,Dups, J.N.,D'Arcy, N.J.,Singh, M.,Chuah, A.,Peat, T.S.,Jackson, C.J.,Cockburn, I.A.
T-dependent B cell responses to Plasmodium induce antibodies that form a high-avidity multivalent complex with the circumsporozoite protein.
PLoS Pathog., 13:e1006469-e1006469, 2017

PubMed Abstract: The repeat region of the Plasmodium falciparum circumsporozoite protein (CSP) is a major vaccine antigen because it can be targeted by parasite neutralizing antibodies; however, little is known about this interaction. We used isothermal titration calorimetry, X-ray crystallography and mutagenesis-validated modeling to analyze the binding of a murine neutralizing antibody to Plasmodium falciparum CSP. Strikingly, we found that the repeat region of CSP is bound by multiple antibodies. This repeating pattern allows multiple weak interactions of single FAB domains to accumulate and yield a complex with a dissociation constant in the low nM range. Because the CSP protein can potentially cross-link multiple B cell receptors (BCRs) we hypothesized that the B cell response might be T cell independent. However, while there was a modest response in mice deficient in T cell help, the bulk of the response was T cell dependent. By sequencing the BCRs of CSP-repeat specific B cells in inbred mice we found that these cells underwent somatic hypermutation and affinity maturation indicative of a T-dependent response. Last, we found that the BCR repertoire of responding B cells was limited suggesting that the structural simplicity of the repeat may limit the breadth of the immune response.

PubMed: 28759640
DOI: 10.1371/journal.ppat.1006469

Experimental method

X-RAY DIFFRACTION (2.52 Å)