6WEZ

Crystal Structure of Broadly Neutralizing Antibody 3I14-D93N Mutant Bound to the Influenza A H3 Hemagglutinin

Summary for 6WEZ

• Entry DOI: 10.2210/pdb6wez/pdb
• Descriptor: Hemagglutinin, heavy chain, light chain, ... (7 entities in total)
• Functional Keywords: antibody, influenza, hemagglutinin, stem epitope, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Influenza A virus; More
• Total number of polymer chains: 4
• Total formula weight: 106182.25

Authors

Harshbarger, W.D.,Lockbaum, G.J.,Deming, D.T.,Attatippaholkun, N.,Schiffer, C.A.,Marasco, W.A. (deposition date: 2020-04-03, release date: 2020-11-25, Last modification date: 2024-04-03)

Primary citation

Harshbarger, W.D.,Deming, D.,Lockbaum, G.J.,Attatippaholkun, N.,Kamkaew, M.,Hou, S.,Somasundaran, M.,Wang, J.P.,Finberg, R.W.,Zhu, Q.K.,Schiffer, C.A.,Marasco, W.A.
Unique structural solution from a V H 3-30 antibody targeting the hemagglutinin stem of influenza A viruses.
Nat Commun, 12:559-559, 2021

PubMed Abstract: Broadly neutralizing antibodies (bnAbs) targeting conserved influenza A virus (IAV) hemagglutinin (HA) epitopes can provide valuable information for accelerating universal vaccine designs. Here, we report structural details for heterosubtypic recognition of HA from circulating and emerging IAVs by the human antibody 3I14. Somatic hypermutations play a critical role in shaping the HCDR3, which alone and uniquely among V3-30 derived antibodies, forms contacts with five sub-pockets within the HA-stem hydrophobic groove. 3I14 light-chain interactions are also key for binding HA and contribute a large buried surface area spanning two HA protomers. Comparison of 3I14 to bnAbs from several defined classes provide insights to the bias selection of V3-30 antibodies and reveals that 3I14 represents a novel structural solution within the V3-30 repertoire. The structures reported here improve our understanding of cross-group heterosubtypic binding activity, providing the basis for advancing immunogen designs aimed at eliciting a broadly protective response to IAV.

PubMed: 33495478
DOI: 10.1038/s41467-020-20879-6

Experimental method

X-RAY DIFFRACTION (3.21 Å)