6XQW

Crystal Structure of MaliM03 Fab in complex with Pfmsp1-19

Summary for 6XQW

• Entry DOI: 10.2210/pdb6xqw/pdb
• Descriptor: MaliM03 Fab Heavy Chain, MaliM03 Fab Light Chain, Pfmsp1-19 (3 entities in total)
• Functional Keywords: fragment binding antigen in complex with protein, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 57967.34

Authors

Singh, S.,Pancera, M. (deposition date: 2020-07-10, release date: 2021-03-03, Last modification date: 2024-10-09)

Primary citation

Thouvenel, C.D.,Fontana, M.F.,Netland, J.,Krishnamurty, A.T.,Takehara, K.K.,Chen, Y.,Singh, S.,Miura, K.,Keitany, G.J.,Lynch, E.M.,Portugal, S.,Miranda, M.C.,King, N.P.,Kollman, J.M.,Crompton, P.D.,Long, C.A.,Pancera, M.,Rawlings, D.J.,Pepper, M.
Multimeric antibodies from antigen-specific human IgM+ memory B cells restrict Plasmodium parasites.
J.Exp.Med., 218:-, 2021

PubMed Abstract: Multimeric immunoglobulin-like molecules arose early in vertebrate evolution, yet the unique contributions of multimeric IgM antibodies to infection control are not well understood. This is partially due to the difficulty of distinguishing low-affinity IgM, secreted rapidly by plasmablasts, from high-affinity antibodies derived from later-arising memory cells. We developed a pipeline to express B cell receptors (BCRs) from Plasmodium falciparum-specific IgM+ and IgG+ human memory B cells (MBCs) as both IgM and IgG molecules. BCRs from both subsets were somatically hypermutated and exhibited comparable monomeric affinity. Crystallization of one IgM+ MBC-derived antibody complexed with antigen defined a linear epitope within a conserved Plasmodium protein. In its physiological multimeric state, this antibody displayed exponentially higher antigen binding than a clonally identical IgG monomer, and more effectively inhibited P. falciparum invasion. Forced multimerization of this IgG significantly improved both antigen binding and parasite restriction, underscoring how avidity can alter antibody function. This work demonstrates the potential of high-avidity IgM in both therapeutics and vaccines.

PubMed: 33661302
DOI: 10.1084/jem.20200942

Experimental method

X-RAY DIFFRACTION (2.991 Å)