PDBsum entry 4uv6

Cell invasion

PDB id: 4uv6

Contents

Protein chains

336 a.a.

Waters ×386

PDB id:

4uv6

Name:

Cell invasion

Title:

Crystal structure of apical membrane antigen 1 from plasmodium knowlesi

Structure:

Apical merozoite antigen 1. Chain: a, b. Fragment: unp residues 43-387. Synonym: ama1. Engineered: yes. Mutation: yes

Source:

Plasmodium knowlesi. Organism_taxid: 5851. Strain: h. Expressed in: pichia pastoris. Expression_system_taxid: 4922.

Resolution:

2.45Å R-factor: 0.172 R-free: 0.227

Authors:

B.Vulliez-Le Normand,F.A.Saul,G.A.Bentley

Key ref:

B.Vulliez-Le Normand et al. (2015). Crystal structure of Plasmodium knowlesi apical membrane antigen 1 and its complex with an invasion-inhibitory monoclonal antibody. Plos One, 10, e0123567. PubMed id: 25886591 DOI: 10.1371/journal.pone.0123567

Date:

04-Aug-14 Release date: 29-Apr-15

Protein chains

A0A384KGX8  (A0A384KGX8_PLAKH) -  Apical membrane antigen 1 from Plasmodium knowlesi (strain H)

Seq: 563 a.a.

Struc: 336 a.a.*

* PDB and UniProt seqs differ at 12 residue positions (black crosses)

DOI no: 10.1371/journal.pone.0123567

Plos One 10:e0123567 (2015)

PubMed id: 25886591

Crystal structure of Plasmodium knowlesi apical membrane antigen 1 and its complex with an invasion-inhibitory monoclonal antibody.

B.Vulliez-Le Normand, B.W.Faber, F.A.Saul, M.van der Eijk, A.W.Thomas, B.Singh, C.H.Kocken, G.A.Bentley.

ABSTRACT

The malaria parasite Plasmodium knowlesi, previously associated only with infection of macaques, is now known to infect humans as well and has become a significant public health problem in Southeast Asia. This species should therefore be targeted in vaccine and therapeutic strategies against human malaria. Apical Membrane Antigen 1 (AMA1), which plays a role in Plasmodium merozoite invasion of the erythrocyte, is currently being pursued in human vaccine trials against P. falciparum. Recent vaccine trials in macaques using the P. knowlesi orthologue PkAMA1 have shown that it protects against infection by this parasite species and thus should be developed for human vaccination as well. Here, we present the crystal structure of Domains 1 and 2 of the PkAMA1 ectodomain, and of its complex with the invasion-inhibitory monoclonal antibody R31C2. The Domain 2 (D2) loop, which is displaced upon binding the Rhoptry Neck Protein 2 (RON2) receptor, makes significant contacts with the antibody. R31C2 inhibits binding of the Rhoptry Neck Protein 2 (RON2) receptor by steric blocking of the hydrophobic groove and by preventing the displacement of the D2 loop which is essential for exposing the complete binding site on AMA1. R31C2 recognizes a non-polymorphic epitope and should thus be cross-strain reactive. PkAMA1 is much less polymorphic than the P. falciparum and P. vivax orthologues. Unlike these two latter species, there are no polymorphic sites close to the RON2-binding site of PkAMA1, suggesting that P. knowlesi has not developed a mechanism of immune escape from the host's humoral response to AMA1.