PDBsum entry 4z80

Membrane protein

PDB id: 4z80

Contents

Protein chains

466 a.a.

32 a.a.

31 a.a.

Ligands

GOL ×4

SO4 ×3

NAG

Waters ×1361

PDB id:

4z80

Name:

Membrane protein

Title:

Crystal structure of toxoplasma gondii ama4 di-dii-egf1 in complex with a 33 aa tgron2l1 peptide

Structure:

Egf family domain-containing protein. Chain: a, b. Fragment: residues 58-553. Engineered: yes. Cytoadherence-linked asexual protein. Chain: c, d. Fragment: residues 1292-1324. Engineered: yes

Source:

Toxoplasma gondii. Organism_taxid: 5811. Gene: tgveg_294330. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Gene: tgveg_294400. Expressed in: escherichia coli. Expression_system_taxid: 511693. Expression_system_cell_line: bl21.

Resolution:

1.53Å R-factor: 0.154 R-free: 0.172

Authors:

M.L.Parker,M.J.Boulanger

Key ref:

M.L.Parker et al. (2016). Dissecting the interface between apicomplexan parasite and host cell: Insights from a divergent AMA-RON2 pair. Proc Natl Acad Sci U S A, 113, 398-403. PubMed id: 26712012 DOI: 10.1073/pnas.1515898113

Date:

08-Apr-15 Release date: 30-Dec-15

Protein chains

S7UIL3  (S7UIL3_TOXGG) -  EGF family domain-containing protein from Toxoplasma gondii (strain ATCC 50853 / GT1)

Seq: 1148 a.a.

Struc: 466 a.a.

Protein chain

B6KQU6  (B6KQU6_TOXGV) -  Cytoadherence-linked asexual protein from Toxoplasma gondii (strain ATCC 50861 / VEG)

Seq: 1490 a.a.

Struc: 32 a.a.

Protein chain

B6KQU6  (B6KQU6_TOXGV) -  Cytoadherence-linked asexual protein from Toxoplasma gondii (strain ATCC 50861 / VEG)

Seq: 1490 a.a.

Struc: 31 a.a.

DOI no: 10.1073/pnas.1515898113

Proc Natl Acad Sci U S A 113:398-403 (2016)

PubMed id: 26712012

Dissecting the interface between apicomplexan parasite and host cell: Insights from a divergent AMA-RON2 pair.

M.L.Parker, D.M.Penarete-Vargas, P.T.Hamilton, A.Guérin, J.P.Dubey, S.J.Perlman, F.Spano, M.Lebrun, M.J.Boulanger.

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.