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34 a.a.
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213 a.a.
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225 a.a.
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* Residue conservation analysis
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PDB id:
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Immune system
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Title:
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Structure of a plasmodium falciparum apical membrane antigen 1-fab f8. 12.19 complex
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Structure:
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Apical membrane antigen 1. Chain: a. Fragment: pfama1 ectoplasmic region, residues 25-605. Synonym: plasmodium falciparum apical membrane antigen 1. Engineered: yes. Mutation: yes. Fab fragment of monoclonal antibody f8.12.19. Chain: b. Fragment: antigen-binding fragment fab, light chain.
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Source:
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Plasmodium falciparum. Organism_taxid: 5833. Strain: fvo. Expressed in: pichia pastoris. Expression_system_taxid: 4922. Mus musculus. Mouse. Organism_taxid: 10090. Strain: balb/c.
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Resolution:
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2.90Å
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R-factor:
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0.215
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R-free:
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0.278
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Authors:
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S.Igonet,B.Vulliez-Le Normand,G.Faure,M.M.Riottot,C.H.M.Kocken, A.W.Thomas,G.A.Bentley
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Key ref:
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S.Igonet
et al.
(2007).
Cross-reactivity studies of an anti-Plasmodium vivax apical membrane antigen 1 monoclonal antibody: binding and structural characterisation.
J Mol Biol,
366,
1523-1537.
PubMed id:
DOI:
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Date:
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18-Sep-06
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Release date:
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30-Jan-07
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PROCHECK
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Headers
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References
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Q9BIM8
(Q9BIM8_PLAFA) -
Apical membrane antigen 1 (Fragment) from Plasmodium falciparum
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Seq:
Struc:
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402 a.a.
34 a.a.*
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DOI no:
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J Mol Biol
366:1523-1537
(2007)
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PubMed id:
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Cross-reactivity studies of an anti-Plasmodium vivax apical membrane antigen 1 monoclonal antibody: binding and structural characterisation.
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S.Igonet,
B.Vulliez-Le Normand,
G.Faure,
M.M.Riottot,
C.H.Kocken,
A.W.Thomas,
G.A.Bentley.
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ABSTRACT
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Apical membrane antigen 1 (AMA1) has an important, but as yet uncharacterised,
role in host cell invasion by the malaria parasite, Plasmodium. The protein,
which is quite conserved between Plasmodium species, comprises an ectoplasmic
region, a single transmembrane segment and a small cytoplasmic domain. The
ectoplasmic region, which can induce protective immunity in animal models of
human malaria, is a leading vaccine candidate that has entered clinical trials.
The monoclonal antibody F8.12.19, raised against the recombinant ectoplasmic
region of AMA1 from Plasmodium vivax, cross-reacts with homologues from
Plasmodium knowlesi, Plasmodium cynomolgi, Plasmodium berghei and Plasmodium
falciparum, as shown by immunofluorescence assays on mature schizonts. The
binding of F8.12.19 to recombinant AMA1 from both P. vivax and P. falciparum was
measured by surface plasmon resonance, revealing an apparent affinity constant
that is about 100-fold weaker for the cross-reacting antigen when compared to
the cognate antigen. Crystal structure analysis of Fab F8.12.19 complexed to
AMA1 from P. vivax and P. falciparum shows that the monoclonal antibody
recognises a discontinuous epitope located on domain III of the ectoplasmic
region, the major component being a loop containing a cystine knot. The
structures provide a basis for understanding the cross-reactivity. Antibody
contacts are made mainly to main-chain and invariant side-chain atoms of AMA1;
contact antigen residues that differ in sequence are located at the periphery of
the antigen-binding site and can be accommodated at the interface between the
two components of the complex. The implications for AMA1 vaccine development are
discussed.
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Selected figure(s)
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Figure 5.
Figure 5. Stereo view of the difference density in the PfAMA1
complex contoured at the 2.5 r.m.s. level. This shows the only
significant residual density in the Fourier maps (located on the
left-hand side of the Figure) that could not be modelled
unambiguously. For clarity, only the antigen is shown. A similar
region of uninterpreted density is present in the difference map
of the PvAMA1 complex.
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Figure 7.
Figure 7. A stereo view of a model of F8.12.19 complexed to
the complete PvAMA1 ectoplasmic region based on superposition of
the PvAMA1 structure (PDB entry 1W8K) onto the complexed PvAMA1
antigen segment. Only the Fv moiety of F8.12.19 is shown for
clarity (ribbon form with V[L] in orange and V[H] in purple).
PvAMA1 is shown as an α-carbon trace with domain I in green,
domain II in blue and domain III in red. The cystine bridges in
PvAMA1 are shown in yellow. This view is identical with that of
Figure 4(a).
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2007,
366,
1523-1537)
copyright 2007.
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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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M.Lamarque,
S.Besteiro,
J.Papoin,
M.Roques,
B.Vulliez-Le Normand,
J.Morlon-Guyot,
J.F.Dubremetz,
S.Fauquenoy,
S.Tomavo,
B.W.Faber,
C.H.Kocken,
A.W.Thomas,
M.J.Boulanger,
G.A.Bentley,
and
M.Lebrun
(2011).
The RON2-AMA1 Interaction is a Critical Step in Moving Junction-Dependent Invasion by Apicomplexan Parasites.
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PLoS Pathog,
7,
e1001276.
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C.Li,
R.Wang,
Y.Wu,
D.Zhang,
Z.He,
and
W.Pan
(2010).
Epitope mapping of PfCP-2.9, an asexual blood-stage vaccine candidate of Plasmodium falciparum.
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Malar J,
9,
94.
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J.Wipasa,
C.Suphavilai,
L.C.Okell,
J.Cook,
P.H.Corran,
K.Thaikla,
W.Liewsaree,
E.M.Riley,
and
J.C.Hafalla
(2010).
Long-lived antibody and B Cell memory responses to the human malaria parasites, Plasmodium falciparum and Plasmodium vivax.
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PLoS Pathog,
6,
e1000770.
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S.Hearty,
P.J.Conroy,
B.V.Ayyar,
B.Byrne,
and
R.O'Kennedy
(2010).
Surface plasmon resonance for vaccine design and efficacy studies: recent applications and future trends.
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Expert Rev Vaccines,
9,
645-664.
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M.R.Galinski,
and
J.W.Barnwell
(2008).
Plasmodium vivax: who cares?
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Malar J,
7,
S9.
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A.M.Coley,
A.Gupta,
V.J.Murphy,
T.Bai,
H.Kim,
R.F.Anders,
M.Foley,
and
A.H.Batchelor
(2007).
Structure of the malaria antigen AMA1 in complex with a growth-inhibitory antibody.
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PLoS Pathog,
3,
1308-1319.
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PDB codes:
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P.Gayathri,
H.Balaram,
and
M.R.Murthy
(2007).
Structural biology of plasmodial proteins.
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Curr Opin Struct Biol,
17,
744-754.
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P.Scheerer,
A.Kramer,
L.Otte,
M.Seifert,
H.Wessner,
C.Scholz,
N.Krauss,
J.Schneider-Mergener,
and
W.Höhne
(2007).
Structure of an anti-cholera toxin antibody Fab in complex with an epitope-derived D-peptide: a case of polyspecific recognition.
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J Mol Recognit,
20,
263-274.
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PDB code:
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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Links
