6OCB

Crystal structure of FluA-20 Fab in complex with the head domain of H3 (A/Hong Kong/1/1968)

Summary for 6OCB

• Entry DOI: 10.2210/pdb6ocb/pdb
• Descriptor: Heavy chain of FluA-20 Fab, Light chain of FluA-20 Fab, Hemagglutinin, ... (5 entities in total)
• Functional Keywords: anti-flu antibody, ha head domain, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 79274.54

Authors

Wilson, I.A.,Lang, S. (deposition date: 2019-03-22, release date: 2019-05-29, Last modification date: 2024-10-23)

Primary citation

Bangaru, S.,Lang, S.,Schotsaert, M.,Vanderven, H.A.,Zhu, X.,Kose, N.,Bombardi, R.,Finn, J.A.,Kent, S.J.,Gilchuk, P.,Gilchuk, I.,Turner, H.L.,Garcia-Sastre, A.,Li, S.,Ward, A.B.,Wilson, I.A.,Crowe Jr., J.E.
A Site of Vulnerability on the Influenza Virus Hemagglutinin Head Domain Trimer Interface.
Cell, 177:1136-1152.e18, 2019

PubMed Abstract: Here, we describe the discovery of a naturally occurring human antibody (Ab), FluA-20, that recognizes a new site of vulnerability on the hemagglutinin (HA) head domain and reacts with most influenza A viruses. Structural characterization of FluA-20 with H1 and H3 head domains revealed a novel epitope in the HA trimer interface, suggesting previously unrecognized dynamic features of the trimeric HA protein. The critical HA residues recognized by FluA-20 remain conserved across most subtypes of influenza A viruses, which explains the Ab's extraordinary breadth. The Ab rapidly disrupted the integrity of HA protein trimers, inhibited cell-to-cell spread of virus in culture, and protected mice against challenge with viruses of H1N1, H3N2, H5N1, or H7N9 subtypes when used as prophylaxis or therapy. The FluA-20 Ab has uncovered an exceedingly conserved protective determinant in the influenza HA head domain trimer interface that is an unexpected new target for anti-influenza therapeutics and vaccines.

PubMed: 31100268
DOI: 10.1016/j.cell.2019.04.011

Experimental method

X-RAY DIFFRACTION (2.1 Å)