4Z80

Crystal structure of Toxoplasma gondii AMA4 DI-DII-EGF1 in complex with a 33 aa TgRON2L1 peptide

4Z80 の概要

• エントリーDOI: 10.2210/pdb4z80/pdb
• 関連するPDBエントリー: 4z81
• 分子名称: EGF family domain-containing protein, Cytoadherence-linked asexual protein, GLYCEROL, ... (6 entities in total)
• 機能のキーワード: apicomplexa, invasion, moving junction, parasite, pan domain, membrane protein
• 由来する生物種: Toxoplasma gondii; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 119462.44

構造登録者

Parker, M.L.,Boulanger, M.J. (登録日: 2015-04-08, 公開日: 2015-12-30, 最終更新日: 2024-10-09)

主引用文献

Parker, M.L.,Penarete-Vargas, D.M.,Hamilton, P.T.,Guerin, A.,Dubey, J.P.,Perlman, S.J.,Spano, F.,Lebrun, M.,Boulanger, M.J.
Dissecting the interface between apicomplexan parasite and host cell: Insights from a divergent AMA-RON2 pair.
Proc.Natl.Acad.Sci.USA, 113:398-403, 2016

PubMed Abstract: Plasmodium falciparum and Toxoplasma gondii are widely studied parasites in phylum Apicomplexa and the etiological agents of severe human malaria and toxoplasmosis, respectively. These intracellular pathogens have evolved a sophisticated invasion strategy that relies on delivery of proteins into the host cell, where parasite-derived rhoptry neck protein 2 (RON2) family members localize to the host outer membrane and serve as ligands for apical membrane antigen (AMA) family surface proteins displayed on the parasite. Recently, we showed that T. gondii harbors a novel AMA designated as TgAMA4 that shows extreme sequence divergence from all characterized AMA family members. Here we show that sporozoite-expressed TgAMA4 clusters in a distinct phylogenetic clade with Plasmodium merozoite apical erythrocyte-binding ligand (MAEBL) proteins and forms a high-affinity, functional complex with its coevolved partner, TgRON2L1. High-resolution crystal structures of TgAMA4 in the apo and TgRON2L1-bound forms complemented with alanine scanning mutagenesis data reveal an unexpected architecture and assembly mechanism relative to previously characterized AMA-RON2 complexes. Principally, TgAMA4 lacks both a deep surface groove and a key surface loop that have been established to govern RON2 ligand binding selectivity in other AMAs. Our study reveals a previously underappreciated level of molecular diversity at the parasite-host-cell interface and offers intriguing insight into the adaptation strategies underlying sporozoite invasion. Moreover, our data offer the potential for improved design of neutralizing therapeutics targeting a broad range of AMA-RON2 pairs and apicomplexan invasive stages.

PubMed: 26712012
DOI: 10.1073/pnas.1515898113

実験手法

X-RAY DIFFRACTION (1.53 Å)