5JW3: Structure Of Medi8852 Fab Fragment In Complex With H7 Ha

Citation:
Abstract
Influenza virus remains a threat because of its ability to evade vaccine-induced immune responses due to antigenic drift. Here, we describe the isolation, evolution, and structure of a broad-spectrum human monoclonal antibody (mAb), MEDI8852, effectively reacting with all influenza A hemagglutinin (HA) subtypes. MEDI8852 uses the heavy-chain VH6-1 gene and has higher potency and breadth when compared to other anti-stem antibodies. MEDI8852 is effective in mice and ferrets with a therapeutic window superior to that of oseltamivir. Crystallographic analysis of Fab alone or in complex with H5 or H7 HA proteins reveals that MEDI8852 binds through a coordinated movement of CDRs to a highly conserved epitope encompassing a hydrophobic groove in the fusion domain and a large portion of the fusion peptide, distinguishing it from other structurally characterized cross-reactive antibodies. The unprecedented breadth and potency of neutralization by MEDI8852 support its development as immunotherapy for influenza virus-infected humans.
PDB ID: 5JW3Download
MMDB ID: 141580
PDB Deposition Date: 2016/5/11
Updated in MMDB: 2016/08
Experimental Method:
x-ray diffraction
Resolution: 3.75  Å
Source Organism:
Influenza A virus (A/turkey/Italy/214845/2002(H7N3))
Similar Structures:
Biological Unit for 5JW3: dodecameric; determined by author and by software (PISA)
Molecular Components in 5JW3
Label Count Molecule
Proteins (12 molecules)
3
Hemagglutinin
Molecule annotation
3
Hemagglutinin
Molecule annotation
3
Medi8852 Heavy Chain
Molecule annotation
3
Medi8852 Light Chain
Molecule annotation
Chemicals (18 molecules)
1
12
2
3
3
3
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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