6AZX

Crystal structure of the neutralizing anti-circumsporozoite protein 663 antibody

Summary for 6AZX

• Entry DOI: 10.2210/pdb6azx/pdb
• Related: 5BK0 5BK3 5BK5 6AZM
• Descriptor: 663 antibody, heavy chain, 663 antibody, light chain (3 entities in total)
• Functional Keywords: malaria, circumsporozoite protein, fab, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 95759.21

Authors

Scally, S.W.,Bosch, A.,Triller, G.,Wardemann, H.,Julien, J.P. (deposition date: 2017-09-13, release date: 2017-12-13, Last modification date: 2024-11-13)

Primary citation

Triller, G.,Scally, S.W.,Costa, G.,Pissarev, M.,Kreschel, C.,Bosch, A.,Marois, E.,Sack, B.K.,Murugan, R.,Salman, A.M.,Janse, C.J.,Khan, S.M.,Kappe, S.H.I.,Adegnika, A.A.,Mordmuller, B.,Levashina, E.A.,Julien, J.P.,Wardemann, H.
Natural Parasite Exposure Induces Protective Human Anti-Malarial Antibodies.
Immunity, 47:1197-1209.e10, 2017

PubMed Abstract: Antibodies against the NANP repeat of circumsporozoite protein (CSP), the major surface antigen of Plasmodium falciparum (Pf) sporozoites, can protect from malaria in animal models but protective humoral immunity is difficult to induce in humans. Here we cloned and characterized rare affinity-matured human NANP-reactive memory B cell antibodies elicited by natural Pf exposure that potently inhibited parasite transmission and development in vivo. We unveiled the molecular details of antibody binding to two distinct protective epitopes within the NANP repeat. NANP repeat recognition was largely mediated by germline encoded and immunoglobulin (Ig) heavy-chain complementarity determining region 3 (HCDR3) residues, whereas affinity maturation contributed predominantly to stabilizing the antigen-binding site conformation. Combined, our findings illustrate the power of exploring human anti-CSP antibody responses to develop tools for malaria control in the mammalian and the mosquito vector and provide a molecular basis for the structure-based design of next-generation CSP malaria vaccines.

PubMed: 29195810
DOI: 10.1016/j.immuni.2017.11.007

Experimental method

X-RAY DIFFRACTION (2.1 Å)