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PDBsum entry 6b0e
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Immune system
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PDB id
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6b0e
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Contents |
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217 a.a.
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216 a.a.
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157 a.a.
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PDB id:
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| Name: |
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Immune system
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Title:
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Crystal structure of pfs25 in complex with the transmission blocking antibody 1260
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Structure:
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1260 antibody, light chain. Chain: a. Engineered: yes. 1260 antibody, heavy chain. Chain: b. Engineered: yes. 25 kda ookinete surface antigen. Chain: e. Synonym: pfs25.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: homo sapiens. Expression_system_taxid: 9606. Plasmodium falciparum. Isolate nf54. Organism_taxid: 5843. Expression_system_taxid: 9606
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Resolution:
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3.30Å
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R-factor:
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0.233
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R-free:
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0.280
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Authors:
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S.W.Scally,B.Mcleod,A.Bosch,C.R.King,J.P.Julien
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Key ref:
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S.W.Scally
et al.
(2017).
Molecular definition of multiple sites of antibody inhibition of malaria transmission-blocking vaccine antigen Pfs25.
Nat Commun,
8,
1568.
PubMed id:
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Date:
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14-Sep-17
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Release date:
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15-Nov-17
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PROCHECK
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Headers
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References
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No UniProt id for this chain
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Nat Commun
8:1568
(2017)
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PubMed id:
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Molecular definition of multiple sites of antibody inhibition of malaria transmission-blocking vaccine antigen Pfs25.
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S.W.Scally,
B.McLeod,
A.Bosch,
K.Miura,
Q.Liang,
S.Carroll,
S.Reponen,
N.Nguyen,
E.Giladi,
S.Rämisch,
V.Yusibov,
A.Bradley,
F.Lemiale,
W.R.Schief,
D.Emerling,
P.Kellam,
C.R.King,
J.P.Julien.
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ABSTRACT
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The Plasmodium falciparum Pfs25 protein (Pfs25) is a leading malaria
transmission-blocking vaccine antigen. Pfs25 vaccination is intended to elicit
antibodies that inhibit parasite development when ingested by Anopheles
mosquitoes during blood meals. The Pfs25 three-dimensional structure has
remained elusive, hampering a molecular understanding of its function and
limiting immunogen design. We report six crystal structures of Pfs25 in complex
with antibodies elicited by immunization via Pfs25 virus-like particles in human
immunoglobulin loci transgenic mice. Our structural findings reveal the fine
specificities associated with two distinct immunogenic sites on Pfs25.
Importantly, one of these sites broadly overlaps with the epitope of the
well-known 4B7 mouse antibody, which can be targeted simultaneously by
antibodies that target a non-overlapping site to additively increase parasite
inhibition. Our molecular characterization of inhibitory antibodies informs on
the natural disposition of Pfs25 on the surface of ookinetes and provides the
structural blueprints to design next-generation immunogens.
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Links
