9YC3

Crystal structure of malaria transmission-blocking antigen PfHAP2 domain 3 in complex with nanobody WNb 334

Summary for 9YC3

• Entry DOI: 10.2210/pdb9yc3/pdb
• Descriptor: Nanobody WNb 334, Male gamete fusion factor HAP2 (3 entities in total)
• Functional Keywords: transmission-blocking, nanobody, fusogen, malaria, protein binding
• Biological source: Vicugna pacos; More
• Total number of polymer chains: 2
• Total formula weight: 30528.15

Authors

Lyons, F.M.T.,Pymm, P.,Dietrich, M.H.,Tham, W.H. (deposition date: 2025-09-18, release date: 2025-12-31, Last modification date: 2026-02-25)

Primary citation

Lyons, F.M.T.,Chmielewski, J.,Chan, L.J.,Gabriela, M.,Chan, R.W.B.,Adair, A.,Tong, J.,Pymm, P.,Zeglinski, K.,Gouil, Q.,Tham, W.H.,Dietrich, M.H.
Crystal structure and nanobodies against domain 3 of the malaria parasite fusogen Plasmodium falciparum HAP2.
Biochem.J., 483:119-133, 2026

PubMed Abstract: Malaria parasites are transmitted to humans through a bite from an infected female Anopheles mosquito. Within the mosquito midgut, malaria parasite gametes are activated and undergo fertilisation. If parasite fertilisation is perturbed, this stops the transmission of malaria parasites from mosquito to human. One proposed target of transmission-blocking interventions is Plasmodium falciparum fusogen PfHAP2, which is essential for gamete fusion during parasite fertilisation. However, to date, no monoclonal antibodies or structures of PfHAP2 have been generated. We have identified nanobodies that bind specifically to domain 3 of PfHAP2 with nanomolar affinities, two of which show some cross-species reactivity with HAP2 of other Plasmodium species. The crystal structure of one nanobody in complex with domain 3 of PfHAP2 provides the first structural insights into this transmission-blocking target in P. falciparum.

PubMed: 41498187
DOI: 10.1042/BCJ20250297

Experimental method

X-RAY DIFFRACTION (2.8 Å)