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Structure paper

TitleDiverse Antibody Responses to Conserved Structural Motifs in Plasmodium falciparum Circumsporozoite Protein.
Journal, issue, pagesJ Mol Biol, Vol. 432, Issue 4, Page 1048-1063, Year 2020
Publish dateFeb 14, 2020
AuthorsTossapol Pholcharee / David Oyen / Jonathan L Torres / Yevel Flores-Garcia / Gregory M Martin / Gonzalo E González-Páez / Daniel Emerling / Wayne Volkmuth / Emily Locke / C Richter King / Fidel Zavala / Andrew B Ward / Ian A Wilson /
PubMed AbstractMalaria vaccine candidate RTS,S/AS01 is based on the central and C-terminal regions of the circumsporozoite protein (CSP) of P. falciparum. mAb397 was isolated from a volunteer in an RTS,S/AS01 ...Malaria vaccine candidate RTS,S/AS01 is based on the central and C-terminal regions of the circumsporozoite protein (CSP) of P. falciparum. mAb397 was isolated from a volunteer in an RTS,S/AS01 clinical trial, and it protects mice from infection by malaria sporozoites. However, mAb397 originates from the less commonly used VH3-15 germline gene compared to the VH3-30/33 antibodies generally elicited by RTS,S to the central NANP repeat region of CSP. The crystal structure of mAb397 with an NPNA peptide shows that the central NPNA forms a type I β-turn and is the main recognition motif. In most anti-NANP antibodies studied to date, a germline-encoded Trp is used to engage the Pro in NPNA β-turns, but here the Trp interacts with the first Asn. This "conserved" Trp, however, can arise from different germline genes and be located in the heavy or the light chain. Variation in the terminal ψ angles of the NPNA β-turns results in different dispositions of the subsequent NPNA and, hence, different stoichiometries and modes of antibody binding to rsCSP. Diverse protective antibodies against NANP repeats are therefore not limited to a single germline gene response or mode of binding.
External linksJ Mol Biol / PubMed:31883801 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.75 - 31.0 Å
Structure data

EMDB-20772:
Fab397 in complex with NPNA8 peptide (Class 1)
Method: EM (single particle) / Resolution: 24.0 Å

EMDB-20773:
Fab397 in complex with NPNA8 peptide (Class 2)
Method: EM (single particle) / Resolution: 21.0 Å

EMDB-20774:
Fab397 in complex with NPNA8 peptide (Class 3)
Method: EM (single particle) / Resolution: 27.0 Å

EMDB-20775:
Fab397 in complex with rsCSP (Class 1)
Method: EM (single particle) / Resolution: 28.0 Å

EMDB-20776:
Fab397 in complex with rsCSP (Class 2)
Method: EM (single particle) / Resolution: 27.0 Å

EMDB-20777:
Fab397 in complex with rsCSP (Class 3)
Method: EM (single particle) / Resolution: 28.0 Å

EMDB-20778:
Fab397 in complex with rsCSP (Class 4)
Method: EM (single particle) / Resolution: 30.0 Å

EMDB-20779:
Fab397 in complex with rsCSP (Class 5)
Method: EM (single particle) / Resolution: 31.0 Å

EMDB-20780:
Fab397 in complex with rsCSP (Class 6)
Method: EM (single particle) / Resolution: 31.0 Å

PDB-6uc5:
Fab397 in complex with NPNA peptide
Method: X-RAY DIFFRACTION / Resolution: 1.75 Å

Chemicals

ChemComp-HOH:
WATER

Source
  • homo sapiens (human)
  • Plasmodium falciparum (malaria parasite P. falciparum)
  • plasmodium falciparum 3d7 (eukaryote)
KeywordsIMMUNE SYSTEM / Antibody / Malaria / Circumsporozoite protein / CSP / NANP / NANP repeats / Plasmodium / Plasmodium falciparum

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