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PDBsum entry 2q8a
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protein Protein-protein interface(s) links
Immune system PDB id
2q8a

 

 

 

 

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JSmol PyMol  
Contents
Protein chains
316 a.a. *
214 a.a. *
199 a.a. *
Waters ×247
* Residue conservation analysis
PDB id:
2q8a
Name: Immune system
Title: Structure of the malaria antigen ama1 in complex with a growth- inhibitory antibody
Structure: Apical membrane antigen 1. Chain: a. Fragment: domains i and ii (residues 104-438). Engineered: yes. 1f9 light chain. Chain: l. 1f9 heavy chain. Chain: h
Source: Plasmodium falciparum. Organism_taxid: 36329. Strain: 3d7. Gene: ama1. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Mus musculus. House mouse. Organism_taxid: 10090.
Resolution:
2.40Å     R-factor:   0.204     R-free:   0.245
Authors: A.Gupta,V.J.Murphy,R.F.Anders,A.H.Batchelor
Key ref: A.M.Coley et al. (2007). Structure of the malaria antigen AMA1 in complex with a growth-inhibitory antibody. Plos Pathog, 3, 1308-1319. PubMed id: 17907804
Date:
10-Jun-07     Release date:   09-Oct-07    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q7KQK5  (Q7KQK5_PLAF7) -  Apical membrane antigen 1 from Plasmodium falciparum (isolate 3D7)
Seq:
Struc: 		 
Seq:
Struc: 		622 a.a.
316 a.a.
Protein chain
No UniProt id for this chain
Struc: 214 a.a.
Protein chain
No UniProt id for this chain
Struc: 199 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
Plos Pathog 3:1308-1319 (2007)
PubMed id: 17907804  
 
 
Structure of the malaria antigen AMA1 in complex with a growth-inhibitory antibody.
A.M.Coley, A.Gupta, V.J.Murphy, T.Bai, H.Kim, M.Foley, R.F.Anders, A.H.Batchelor.
 
  ABSTRACT  
 
Identifying functionally critical regions of the malaria antigen AMA1 (apical membrane antigen 1) is necessary to understand the significance of the polymorphisms within this antigen for vaccine development. The crystal structure of AMA1 in complex with the Fab fragment of inhibitory monoclonal antibody 1F9 reveals that 1F9 binds to the AMA1 solvent-exposed hydrophobic trough, confirming its importance. 1F9 uses the heavy and light chain complementarity-determining regions (CDRs) to wrap around the polymorphic loops adjacent to the trough, but uses a ridge of framework residues to bind to the hydrophobic trough. The resulting 1F9-AMA1-combined buried surface of 2,470 A(2) is considerably larger than previously reported Fab-antigen interfaces. Mutations of polymorphic AMA1 residues within the 1F9 epitope disrupt 1F9 binding and dramatically reduce the binding of affinity-purified human antibodies. Moreover, 1F9 binding to AMA1 is competed by naturally acquired human antibodies, confirming that the 1F9 epitope is a frequent target of immunological attack.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21292899 I.Soulama, J.D.Bigoga, M.Ndiaye, E.C.Bougouma, J.Quagraine, P.N.Casimiro, T.T.Stedman, and S.B.Sirima (2011).
Genetic diversity of polymorphic vaccine candidate antigens (apical membrane antigen-1, merozoite surface protein-3, and erythrocyte binding antigen-175) in Plasmodium falciparum isolates from western and central Africa.
  Am J Trop Med Hyg, 84, 276-284.  
20097151 B.Singh, M.Cabrera-Mora, J.Jiang, M.Galinski, and A.Moreno (2010).
Genetic linkage of autologous T cell epitopes in a chimeric recombinant construct improves anti-parasite and anti-disease protective effect of a malaria vaccine candidate.
  Vaccine, 28, 2580-2592.  
20228060 D.Richard, C.A.MacRaild, D.T.Riglar, J.A.Chan, M.Foley, J.Baum, S.A.Ralph, R.S.Norton, and A.F.Cowman (2010).
Interaction between Plasmodium falciparum apical membrane antigen 1 and the rhoptry neck protein complex defines a key step in the erythrocyte invasion process of malaria parasites.
  J Biol Chem, 285, 14815-14822.  
20732997 F.H.Osier, G.D.Weedall, F.Verra, L.Murungi, K.K.Tetteh, P.Bull, B.W.Faber, E.Remarque, A.Thomas, K.Marsh, and D.J.Conway (2010).
Allelic diversity and naturally acquired allele-specific antibody responses to Plasmodium falciparum apical membrane antigen 1 in Kenya.
  Infect Immun, 78, 4625-4633.  
19948834 S.Dutta, L.S.Dlugosz, J.W.Clayton, C.D.Pool, J.D.Haynes, R.A.Gasser, and A.H.Batchelor (2010).
Alanine mutagenesis of the primary antigenic escape residue cluster, c1, of apical membrane antigen 1.
  Infect Immun, 78, 661-671.  
19417768 J.S.Richards, and J.G.Beeson (2009).
The future for blood-stage vaccines against malaria.
  Immunol Cell Biol, 87, 377-390.  
19164290 K.S.Harris, J.L.Casey, A.M.Coley, J.A.Karas, J.K.Sabo, Y.Y.Tan, O.Dolezal, R.S.Norton, A.B.Hughes, D.Scanlon, and M.Foley (2009).
Rapid optimization of a peptide inhibitor of malaria parasite invasion by comprehensive N-methyl scanning.
  J Biol Chem, 284, 9361-9371.  
  20165550 S.L.Takala, D.Coulibaly, M.A.Thera, A.H.Batchelor, M.P.Cummings, A.A.Escalante, A.Ouattara, K.Traoré, A.Niangaly, A.A.Djimdé, O.K.Doumbo, and C.V.Plowe (2009).
Extreme polymorphism in a vaccine antigen and risk of clinical malaria: implications for vaccine development.
  Sci Transl Med, 1, 2ra5.  
18495848 D.Quelhas, L.Puyol, L.Quintó, E.Serra-Casas, T.Nhampossa, E.Macete, P.Aide, A.Mayor, I.Mandomando, S.Sanz, J.J.Aponte, V.S.Chauhan, C.E.Chitnis, P.L.Alonso, C.Menéndez, and C.Dobaño (2008).
Impact of intermittent preventive treatment with sulfadoxine-pyrimethamine on antibody responses to erythrocytic-stage Plasmodium falciparum antigens in infants in Mozambique.
  Clin Vaccine Immunol, 15, 1282-1291.  
18958278 F.J.McCallum, K.E.Persson, C.K.Mugyenyi, F.J.Fowkes, J.A.Simpson, J.S.Richards, T.N.Williams, K.Marsh, and J.G.Beeson (2008).
Acquisition of growth-inhibitory antibodies against blood-stage Plasmodium falciparum.
  PLoS ONE, 3, e3571.  
18031585 S.Garg, M.T.Alam, M.K.Das, V.Dev, A.Kumar, A.P.Dash, and Y.D.Sharma (2007).
Sequence diversity and natural selection at domain I of the apical membrane antigen 1 among Indian Plasmodium falciparum populations.
  Malar J, 6, 154.  
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.

 

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