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PDBsum entry 6o2c

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protein ligands Protein-protein interface(s) links
Immune system PDB id
6o2c

 

 

 

 

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Contents
Protein chains
225 a.a.
215 a.a.
121 a.a.
11 a.a.
Ligands
EDO ×6
PGE
PEG
Waters ×441
PDB id:
6o2c
Name: Immune system
Title: Crystal structure of 4493 fab in complex with circumsporozoite protein nanp3 and anti-kappa vhh domain
Structure: 4493 fab heavy chain. Chain: a. Engineered: yes. 4493 kappa light chain. Chain: b. Engineered: yes. Anti-kappa vhh domain. Chain: k. Engineered: yes.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: homo sapiens. Expression_system_taxid: 9606. Lama glama. Llama. Organism_taxid: 9844. Expressed in: escherichia coli.
Resolution:
2.02Å     R-factor:   0.163     R-free:   0.195
Authors: S.W.Scally,A.Bosch,K.Prieto,R.Murugan,H.Wardemann,J.P.Julien
Key ref: R.Murugan et al. (2020). Evolution of protective human antibodies against Plasmodium falciparum circumsporozoite protein repeat motifs. Nat Med, 26, 1135-1145. PubMed id: 32451496 DOI: 10.1038/s41591-020-0881-9
Date:
22-Feb-19     Release date:   01-Jul-20    
PROCHECK
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 Headers
 References

Protein chain
No UniProt id for this chain
Struc: 225 a.a.
Protein chain
No UniProt id for this chain
Struc: 215 a.a.
Protein chain
No UniProt id for this chain
Struc: 121 a.a.
Protein chain
Pfam   ArchSchema ?
P19597  (CSP_PLAFO) -  Circumsporozoite protein from Plasmodium falciparum (isolate NF54)
Seq:
Struc:
397 a.a.
11 a.a.
Key:    PfamA domain  Secondary structure

 

 
DOI no: 10.1038/s41591-020-0881-9 Nat Med 26:1135-1145 (2020)
PubMed id: 32451496  
 
 
Evolution of protective human antibodies against Plasmodium falciparum circumsporozoite protein repeat motifs.
R.Murugan, S.W.Scally, G.Costa, G.Mustafa, E.Thai, T.Decker, A.Bosch, K.Prieto, E.A.Levashina, J.P.Julien, H.Wardemann.
 
  ABSTRACT  
 
The circumsporozoite protein of the human malaria parasite Plasmodium falciparum (PfCSP) is the main target of antibodies that prevent the infection and disease, as shown in animal models. However, the limited efficacy of the PfCSP-based vaccine RTS,S calls for a better understanding of the mechanisms driving the development of the most potent human PfCSP antibodies and identification of their target epitopes. By characterizing 200 human monoclonal PfCSP antibodies induced by sporozoite immunization, we establish that the most potent antibodies bind around a conserved (N/D)PNANPN(V/A) core. High antibody affinity to the core correlates with protection from parasitemia in mice and evolves around the recognition of NANP motifs. The data suggest that the rational design of a next-generation PfCSP vaccine that elicits high-affinity antibody responses against the core epitope will promote the induction of protective humoral immune responses.
 

 

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