PDBsum entry 1yxe

Immune system

PDB id: 1yxe

Contents

Protein chain

140 a.a. *

* Residue conservation analysis

PDB id:

1yxe

Name:

Immune system

Title:

Structure and inter-domain interactions of domain ii from the blood stage malarial protein, apical membrane antigen 1

Structure:

Apical membrane antigen 1. Chain: a. Engineered: yes

Source:

Plasmodium falciparum. Organism_taxid: 36329. Strain: 3d7. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

NMR struc:

20 models

Authors:

Z.P.Feng,D.W.Keizer,R.A.Stevenson,S.Yao,J.J.Babon,V.J.Murphy, R.F.Anders,R.S.Norton

Key ref:

Z.P.Feng et al. (2005). Structure and inter-domain interactions of domain II from the blood-stage malarial protein, apical membrane antigen 1. J Mol Biol, 350, 641-656. PubMed id: 15964019 DOI: 10.1016/j.jmb.2005.05.011

Date:

21-Feb-05 Release date: 05-Jul-05

Protein chain

P22621  (AMA1_PLAFF) -  Apical membrane antigen 1 from Plasmodium falciparum (isolate FC27 / Papua New Guinea)

Seq: 622 a.a.

Struc: 140 a.a.*

* PDB and UniProt seqs differ at 13 residue positions (black crosses)

DOI no: 10.1016/j.jmb.2005.05.011

J Mol Biol 350:641-656 (2005)

PubMed id: 15964019

Structure and inter-domain interactions of domain II from the blood-stage malarial protein, apical membrane antigen 1.

Z.P.Feng, D.W.Keizer, R.A.Stevenson, S.Yao, J.J.Babon, V.J.Murphy, R.F.Anders, R.S.Norton.

ABSTRACT

The malarial surface antigen apical membrane antigen (AMA1), from Plasmodium falciparum, is a leading candidate for inclusion in a vaccine against malaria. AMA1 is synthesised by mature blood-stages of the parasite and is located initially in the apical organelles of the merozoite. Prior to merozoite invasion of host erythrocytes, it is processed into a 66 kDa type 1 integral membrane protein on the merozoite surface. The pattern of disulphide bonds in AMA1 has been the basis for separation of the ectodomain into three domains, with three, two and three disulphide bonds, respectively. We have determined the solution structure of a 16kDa construct corresponding to the putative second domain of AMA1. While circular dichroism and hydrodynamic data were consistent with a folded structure for domain II, its NMR spectra were characterised by broad lines and significant peak overlap, more typical of a molten globule. Consistent with this, domain II bound the fluorescent dye 8-anilino-1-naphthalene sulphonate (ANS). We have nonetheless determined a structure, which defines the secondary structure elements and global fold. The two disulphide bonds link the N and C-terminal regions of the molecule, which come together to form a four-stranded beta-sheet linked to a short helix. A long loop linking the N and C-terminal regions contains four other alpha-helices, the locations of which are not fixed relative to the beta-sheet core, even though they are well-defined locally. Very recently this region of domain II has been shown to contain the epitope recognised by the invasion-inhibitory antibody 4G2, even though it does not contain any of the polymorphisms that are regarded as having arisen in response to the pressure of immune recognition.

Selected figure(s)

Figure 1.
Figure 1. AMA1 sequence. Schematic of PfAMA1 ectodomain, showing the three putative domains, I, II and III, and the locations of the eight disulphide bridges. Residues shaded in red represent mutations across 11 different naturally occurring P. falciparum sequences. The boundaries of our domain II construct are indicated by arrows. This Figure was modified from Hodder et al.9

Figure 5.
Figure 5. Structure of domain II. (a) Stereo view of the family of 20 structures, superimposed over backbone heavy atoms for the b-sheet core; only residues from N309-D348 and W399-A430 are shown. (b) Ribbon view of the closest-to-average structure highlighting the a-helix, b-sheet, two disulphides (orange) and four polymorphic residues (blue). This Figure was prepared using MOLMOL.65

The above figures are reprinted by permission from Elsevier: J Mol Biol (2005, 350, 641-656) copyright 2005.

Figures were selected by an automated process.