5CJS

Crystal structure of a monomeric influenza hemagglutinin stem in complex with an broadly neutralizing antibody CR9114


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 4.30 Å
  • R-Value Free: 0.303 
  • R-Value Work: 0.262 
  • R-Value Observed: 0.264 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

A stable trimeric influenza hemagglutinin stem as a broadly protective immunogen.

Impagliazzo, A.Milder, F.Kuipers, H.Wagner, M.V.Zhu, X.Hoffman, R.M.van Meersbergen, R.Huizingh, J.Wanningen, P.Verspuij, J.de Man, M.Ding, Z.Apetri, A.Kukrer, B.Sneekes-Vriese, E.Tomkiewicz, D.Laursen, N.S.Lee, P.S.Zakrzewska, A.Dekking, L.Tolboom, J.Tettero, L.van Meerten, S.Yu, W.Koudstaal, W.Goudsmit, J.Ward, A.B.Meijberg, W.Wilson, I.A.Radosevic, K.

(2015) Science 349: 1301-1306

  • DOI: https://doi.org/10.1126/science.aac7263
  • Primary Citation of Related Structures:  
    5CJQ, 5CJS

  • PubMed Abstract: 

    The identification of human broadly neutralizing antibodies (bnAbs) targeting the hemagglutinin (HA) stem revitalized hopes of developing a universal influenza vaccine. Using a rational design and library approach, we engineered stable HA stem antigens ("mini-HAs") based on an H1 subtype sequence. Our most advanced candidate exhibits structural and bnAb binding properties comparable to those of full-length HA, completely protects mice in lethal heterologous and heterosubtypic challenge models, and reduces fever after sublethal challenge in cynomolgus monkeys. Antibodies elicited by this mini-HA in mice and nonhuman primates bound a wide range of HAs, competed with human bnAbs for HA stem binding, neutralized H5N1 viruses, and mediated antibody-dependent effector activity. These results represent a proof of concept for the design of HA stem mimics that elicit bnAbs against influenza A group 1 viruses.


  • Organizational Affiliation

    Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Archimedesweg 4-6, 2301 CA Leiden, Netherlands. aimpagli@its.jnj.com wilson@scripps.edu.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
CR9114 light chainA [auth L],
E
215Homo sapiensMutation(s): 0 
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
CR9114 heavy chainB [auth H],
F
230Homo sapiensMutation(s): 0 
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Designed influenza hemagglutinin stem #4454, HA1C,
G [auth J]
62synthetic constructMutation(s): 0 
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
Designed influenza hemagglutinin stem #4454, HA2D,
H [auth K]
191synthetic constructMutation(s): 0 
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 4.30 Å
  • R-Value Free: 0.303 
  • R-Value Work: 0.262 
  • R-Value Observed: 0.264 
  • Space Group: P 32 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 110.869α = 90
b = 110.869β = 90
c = 359.161γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-09-09
    Type: Initial release
  • Version 1.1: 2015-09-30
    Changes: Database references
  • Version 1.2: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Database references, Derived calculations, Structure summary