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TitleCryo-EM structure of circumsporozoite protein with a vaccine-elicited antibody is stabilized by somatically mutated inter-Fab contacts.
Journal, issue, pagesSci Adv, Vol. 4, Issue 10, Page eaau8529, Year 2018
Publish dateOct 10, 2018
AuthorsDavid Oyen / Jonathan L Torres / Christopher A Cottrell / C Richter King / Ian A Wilson / Andrew B Ward /
PubMed AbstractThe circumsporozoite protein (CSP) on the surface of sporozoites is important for parasite development, motility, and host hepatocyte invasion. However, intrinsic disorder of the NANP repeat ...The circumsporozoite protein (CSP) on the surface of sporozoites is important for parasite development, motility, and host hepatocyte invasion. However, intrinsic disorder of the NANP repeat sequence in the central region of CSP has hindered its structural and functional characterization. Here, the cryo-electron microscopy structure at ~3.4-Å resolution of a recombinant shortened CSP construct with the variable domains (Fabs) of a highly protective monoclonal antibody reveals an extended spiral conformation of the central NANP repeat region surrounded by antibodies. This unusual structure appears to be stabilized and/or induced by interaction with an antibody where contacts between adjacent Fabs are somatically mutated and enhance the interaction. This maturation in non-antigen contact residues may be an effective mechanism for antibodies to target tandem repeat sequences and provide novel insights into malaria vaccine design.
External linksSci Adv / PubMed:30324137 / PubMed Central
MethodsEM (single particle)
Resolution3.37 - 27.0 Å
Structure data

EMDB-7897:
Full-length Plasmodium falciparum Circumsporozoite Protein (CSP) in complex with fragment antigen binding (Fab) 311.
Method: EM (single particle) / Resolution: 27.0 Å

EMDB-7898:
recombinant, shortened Plasmodium falciparum Circumsporozoite Protein (CSP) in complex with immunoglobulin g (IgG) 311 .
Method: EM (single particle) / Resolution: 27.0 Å

EMDB-7899:
Recombinant, shortened Plasmodium falciparum Cisrcumsporozoite Protein (rsCSP) in complex with fragment antigen binding (Fab) 317
Method: EM (single particle) / Resolution: 14.0 Å

9065

6mb3

EMDB-9065, PDB-6mb3:
Cryo-EM structure of the circumsporozoite protein of Plasmodium falciparum with a vaccine-elicited antibody reveals maturation of inter-antibody contacts
Method: EM (single particle) / Resolution: 3.37 Å

9114

6mhg

EMDB-9114, PDB-6mhg:
Cryo-EM structure of the circumsporozoite protein of Plasmodium falciparum with a vaccine-elicited antibody reveals maturation of inter-antibody contacts
Method: EM (single particle) / Resolution: 3.57 Å

Source
  • plasmodium falciparum (malaria parasite P. falciparum)
  • homo sapiens (human)
KeywordsIMMUNE SYSTEM / Plasmodium falciparum / antibody / CSP / rsCSP

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