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TitleCryoEM Structure of an Influenza Virus Receptor-Binding Site Antibody-Antigen Interface.
Journal, issue, pagesJ Mol Biol, Vol. 429, Issue 12, Page 1829-1839, Year 2017
Publish dateJun 16, 2017
AuthorsYuhang Liu / Junhua Pan / Simon Jenni / Donald D Raymond / Tim Caradonna / Khoi T Do / Aaron G Schmidt / Stephen C Harrison / Nikolaus Grigorieff /
PubMed AbstractStructure-based vaccine design depends on extensive structural analyses of antigen-antibody complexes.Single-particle electron cryomicroscopy (cryoEM) can circumvent some of the problems of x-ray ...Structure-based vaccine design depends on extensive structural analyses of antigen-antibody complexes.Single-particle electron cryomicroscopy (cryoEM) can circumvent some of the problems of x-ray crystallography as a pipeline for obtaining the required structures. We have examined the potential of single-particle cryoEM for determining the structure of influenza-virus hemagglutinin (HA):single-chain variable-domain fragment complexes, by studying a complex we failed to crystallize in pursuing an extended project on the human immune response to influenza vaccines.The result shows that a combination of cryoEM and molecular modeling can yield details of the antigen-antibody interface, although small variation in the twist of the rod-likeHA trimer limited the overall resolution to about 4.5Å.Comparison of principal 3D classes suggests ways to modify the HA trimer to overcome this limitation. A closely related antibody from the same donor did yield crystals when bound with the same HA, giving us an independent validation of the cryoEM results.The two structures also augment our understanding of receptor-binding site recognition by antibodies that neutralize a wide range of influenza-virus variants.
External linksJ Mol Biol / PubMed:28506635 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution3.4 - 4.8 Å
Structure data

8561

5ujz

EMDB-8561, PDB-5ujz:
CryoEM structure of an influenza virus receptor-binding site antibody-antigen interface - Class 1
Method: EM (single particle) / Resolution: 4.8 Å

8562

5uk0

EMDB-8562, PDB-5uk0:
CryoEM structure of an influenza virus receptor-binding site antibody-antigen interface - Class 2
Method: EM (single particle) / Resolution: 4.8 Å

8563

5uk1

EMDB-8563, PDB-5uk1:
CryoEM structure of an influenza virus receptor-binding site antibody-antigen interface - Class 3
Method: EM (single particle) / Resolution: 4.8 Å

8564

5uk2

EMDB-8564, PDB-5uk2:
CryoEM structure of an influenza virus receptor-binding site antibody-antigen interface - Class 4
Method: EM (single particle) / Resolution: 4.8 Å

PDB-5ug0:
Human antibody H2897 in complex with influenza hemagglutinin H1 Solomon Islands/03/2006
Method: X-RAY DIFFRACTION / Resolution: 3.4 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • influenza a virus (a/solomon islands/3/2006(h1n1))
  • influenza a virus
  • homo sapiens (human)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / Influenza HA / antibody / complex / VIRAL PROTEIN-IMMUNE SYSTEM complex / Viral glycoprotein / Hemagglutinin / Antibody fragment

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