4wz9

APN1 from Anopheles gambiae

spinqualitylabelsall models 4wz9, resolution 2.65Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4wz9 is a 4 chain structure with sequence from Anopheles gambiae and Drosophila. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.65Å Ligands: CU, GOL, NHE, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function AMPN_ANOGA Publication Abstract from PubMed 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-A 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. The Anopheles-midgut APN1 structure reveals a new malaria transmission-blocking vaccine epitope.,Atkinson SC, Armistead JS, Mathias DK, Sandeu MM, Tao D, Borhani-Dizaji N, Tarimo BB, Morlais I, Dinglasan RR, Borg NA Nat Struct Mol Biol. 2015 Jun 15. doi: 10.1038/nsmb.3048. PMID:26075520 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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