6B5T

Structure of PfCSP peptide 29 with human antibody CIS42


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.22 Å
  • R-Value Free: 0.209 
  • R-Value Work: 0.183 
  • R-Value Observed: 0.184 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

A human monoclonal antibody prevents malaria infection by targeting a new site of vulnerability on the parasite.

Kisalu, N.K.Idris, A.H.Weidle, C.Flores-Garcia, Y.Flynn, B.J.Sack, B.K.Murphy, S.Schon, A.Freire, E.Francica, J.R.Miller, A.B.Gregory, J.March, S.Liao, H.X.Haynes, B.F.Wiehe, K.Trama, A.M.Saunders, K.O.Gladden, M.A.Monroe, A.Bonsignori, M.Kanekiyo, M.Wheatley, A.K.McDermott, A.B.Farney, S.K.Chuang, G.Y.Zhang, B.Kc, N.Chakravarty, S.Kwong, P.D.Sinnis, P.Bhatia, S.N.Kappe, S.H.I.Sim, B.K.L.Hoffman, S.L.Zavala, F.Pancera, M.Seder, R.A.

(2018) Nat Med 24: 408-416

  • DOI: https://doi.org/10.1038/nm.4512
  • Primary Citation of Related Structures:  
    6B5L, 6B5M, 6B5N, 6B5O, 6B5P, 6B5R, 6B5S, 6B5T

  • PubMed Abstract: 

    Development of a highly effective vaccine or antibodies for the prevention and ultimately elimination of malaria is urgently needed. Here we report the isolation of a number of human monoclonal antibodies directed against the Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP) from several subjects immunized with an attenuated Pf whole-sporozoite (SPZ) vaccine (Sanaria PfSPZ Vaccine). Passive transfer of one of these antibodies, monoclonal antibody CIS43, conferred high-level, sterile protection in two different mouse models of malaria infection. The affinity and stoichiometry of CIS43 binding to PfCSP indicate that there are two sequential multivalent binding events encompassing the repeat domain. The first binding event is to a unique 'junctional' epitope positioned between the N terminus and the central repeat domain of PfCSP. Moreover, CIS43 prevented proteolytic cleavage of PfCSP on PfSPZ. Analysis of crystal structures of the CIS43 antigen-binding fragment in complex with the junctional epitope determined the molecular interactions of binding, revealed the epitope's conformational flexibility and defined Asn-Pro-Asn (NPN) as the structural repeat motif. The demonstration that CIS43 is highly effective for passive prevention of malaria has potential application for use in travelers, military personnel and elimination campaigns and identifies a new and conserved site of vulnerability on PfCSP for next-generation rational vaccine design.


  • Organizational Affiliation

    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.


Macromolecules

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
pfCSP peptide 29: ALA-ASN-PRO-ASN-ALA-ASN-PRO-ASN-ALA-ASN-PRO-ASN-ALA15Plasmodium falciparumMutation(s): 0 
UniProt
Find proteins for P02893 (Plasmodium falciparum)
Explore P02893 
Go to UniProtKB:  P02893
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP02893
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
CIS42 Fab Heavy chainB [auth H]222Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
CIS42 Fab Light chainC [auth L]216Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NH4
Query on NH4

Download Ideal Coordinates CCD File 
D [auth L]AMMONIUM ION
H4 N
QGZKDVFQNNGYKY-UHFFFAOYSA-O
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
PCA
Query on PCA
B [auth H]L-PEPTIDE LINKINGC5 H7 N O3GLN
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.22 Å
  • R-Value Free: 0.209 
  • R-Value Work: 0.183 
  • R-Value Observed: 0.184 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 41.58α = 90
b = 70.664β = 90
c = 163.363γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2018-03-21
    Type: Initial release
  • Version 1.1: 2018-04-04
    Changes: Data collection, Database references
  • Version 1.2: 2018-04-25
    Changes: Data collection, Database references