8uwa

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VH1-18 QxxV class antibody 09-1B12 bound to A/Perth/16/2009 H3N2 hemagglutininVH1-18 QxxV class antibody 09-1B12 bound to A/Perth/16/2009 H3N2 hemagglutinin

Structural highlights

8uwa is a 9 chain structure with sequence from Homo sapiens and Influenza A virus (A/Perth/16/2009(H3N2)). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 4.02Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

Broadly neutralizing antibodies (bnAbs) targeting the hemagglutinin (HA) stem of influenza A viruses (IAVs) tend to be effective against either group 1 or group 2 viral diversity. In rarer cases, intergroup protective bnAbs can be generated by human antibody paratopes that accommodate the conserved glycan differences between the group 1 and group 2 stems. We applied germline-engaging nanoparticle immunogens to elicit a class of cross-group bnAbs from physiological precursor frequency within a humanized mouse model. Cross-group protection depended on the presence of the human bnAb precursors within the B cell repertoire, and the vaccine-expanded antibodies enriched for an N55T substitution in the CDRH2 loop, a hallmark of the bnAb class. Structurally, this single mutation introduced a flexible fulcrum to accommodate glycosylation differences and could alone enable cross-group protection. Thus, broad IAV immunity can be expanded from the germline repertoire via minimal antigenic input and an exceptionally simple antibody development pathway.

Eliciting a single amino acid change by vaccination generates antibody protection against group 1 and group 2 influenza A viruses.,Ray R, Nait Mohamed FA, Maurer DP, Huang J, Alpay BA, Ronsard L, Xie Z, Han J, Fernandez-Quintero M, Phan QA, Ursin RL, Vu M, Kirsch KH, Prum T, Rosado VC, Bracamonte-Moreno T, Okonkwo V, Bals J, McCarthy C, Nair U, Kanekiyo M, Ward AB, Schmidt AG, Batista FD, Lingwood D Immunity. 2024 Apr 18:S1074-7613(24)00143-2. doi: 10.1016/j.immuni.2024.03.022. PMID:38670113[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. Ray R, Nait Mohamed FA, Maurer DP, Huang J, Alpay BA, Ronsard L, Xie Z, Han J, Fernandez-Quintero M, Phan QA, Ursin RL, Vu M, Kirsch KH, Prum T, Rosado VC, Bracamonte-Moreno T, Okonkwo V, Bals J, McCarthy C, Nair U, Kanekiyo M, Ward AB, Schmidt AG, Batista FD, Lingwood D. Eliciting a single amino acid change by vaccination generates antibody protection against group 1 and group 2 influenza A viruses. Immunity. 2024 Apr 18:S1074-7613(24)00143-2. PMID:38670113 doi:10.1016/j.immuni.2024.03.022

8uwa, resolution 4.02Å

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OCA