6WJ1

Crystal structure of Fab 54-4H03 bound to H1 influenza hemagglutinin

Summary for 6WJ1

• Entry DOI: 10.2210/pdb6wj1/pdb
• Descriptor: Hemagglutinin HA1 chain, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (11 entities in total)
• Functional Keywords: antibody, influenza hemagglutinin, immune system
• Biological source: Influenza A virus; More
• Total number of polymer chains: 12
• Total formula weight: 322238.58

Authors

Wu, N.C.,Wilson, I.A. (deposition date: 2020-04-11, release date: 2020-07-01, Last modification date: 2024-10-16)

Primary citation

Wu, N.C.,Andrews, S.F.,Raab, J.E.,O'Connell, S.,Schramm, C.A.,Ding, X.,Chambers, M.J.,Leung, K.,Wang, L.,Zhang, Y.,Mascola, J.R.,Douek, D.C.,Ledgerwood, J.E.,McDermott, A.B.,Wilson, I.A.
Convergent Evolution in Breadth of Two VH6-1-Encoded Influenza Antibody Clonotypes from a Single Donor.
Cell Host Microbe, 28:434-, 2020

PubMed Abstract: Understanding how broadly neutralizing antibodies (bnAbs) to influenza hemagglutinin (HA) naturally develop in humans is critical to the design of universal influenza vaccines. Several classes of bnAbs directed to the conserved HA stem were found in multiple individuals, including one encoded by heavy-chain variable domain V6-1. We describe two genetically similar V6-1 bnAb clonotypes from the same individual that exhibit different developmental paths toward broad neutralization activity. One clonotype evolved from a germline precursor recognizing influenza group 1 subtypes to gain breadth to group 2 subtypes. The other clonotype recognized group 2 subtypes and developed binding to group 1 subtypes through somatic hypermutation. Crystal structures reveal that the specificity differences are primarily mediated by complementarity-determining region H3 (CDR H3). Thus, while V6-1 provides a framework for development of HA stem-directed bnAbs, sequence differences in CDR H3 junctional regions during VDJ recombination can alter reactivity and evolutionary pathways toward increased breadth.

PubMed: 32619441
DOI: 10.1016/j.chom.2020.06.003

Experimental method

X-RAY DIFFRACTION (3.503 Å)