4WZ9

APN1 from Anopheles gambiae

Summary for 4WZ9

• Entry DOI: 10.2210/pdb4wz9/pdb
• Descriptor: AGAP004809-PA, ALA-ALA-ALA-LYS-ALA, ALA-ALA-LYS, ... (8 entities in total)
• Functional Keywords: aminopeptidase, metalloprotease, hydrolase
• Biological source: Anopheles gambiae (African malaria mosquito); More
• Total number of polymer chains: 4
• Total formula weight: 216470.09

Authors

Atkinson, S.C.,Armistead, J.S.,Mathias, D.K.,Sandeu, M.M.,Tao, D.,Borhani-Dizaji, N.,Morlais, I.,Dinglasan, R.R.,Borg, N.A. (deposition date: 2014-11-19, release date: 2015-06-17, Last modification date: 2024-10-23)

Primary citation

Atkinson, S.C.,Armistead, J.S.,Mathias, D.K.,Sandeu, M.M.,Tao, D.,Borhani-Dizaji, N.,Tarimo, B.B.,Morlais, I.,Dinglasan, R.R.,Borg, N.A.
The Anopheles-midgut APN1 structure reveals a new malaria transmission-blocking vaccine epitope.
Nat.Struct.Mol.Biol., 22:532-539, 2015

PubMed Abstract: Mosquito-based malaria transmission-blocking vaccines (mTBVs) target midgut-surface antigens of the Plasmodium parasite's obligate vector, the Anopheles mosquito. The alanyl aminopeptidase N (AnAPN1) is the leading mTBV immunogen; however, AnAPN1's role in Plasmodium infection of the mosquito and how anti-AnAPN1 antibodies functionally block parasite transmission have remained elusive. Here we present the 2.65-Å crystal structure of AnAPN1 and the immunoreactivity and transmission-blocking profiles of three monoclonal antibodies (mAbs) to AnAPN1, including mAb 4H5B7, which effectively blocks transmission of natural strains of Plasmodium falciparum. Using the AnAPN1 structure, we map the conformation-dependent 4H5B7 neoepitope to a previously uncharacterized region on domain 1 and further demonstrate that nonhuman-primate neoepitope-specific IgG also blocks parasite transmission. We discuss the prospect of a new biological function of AnAPN1 as a receptor for Plasmodium in the mosquito midgut and the implications for redesigning the AnAPN1 mTBV.

PubMed: 26075520
DOI: 10.1038/nsmb.3048

Experimental method

X-RAY DIFFRACTION (2.65 Å)