4HKX

Influenza hemagglutinin in complex with CH67 Fab

Summary for 4HKX

• Entry DOI: 10.2210/pdb4hkx/pdb
• Related: 4HK0 4HK3 4HKB
• Descriptor: Hemagglutinin HA1, CH67 heavy chain, CH67 light chain, ... (5 entities in total)
• Functional Keywords: fab fragment, viral protein-immune system complex, viral protein/immune system
• Biological source: Influenza A virus; More
• Total number of polymer chains: 3
• Total formula weight: 73037.07

Authors

Schmidt, A.G.,Harrison, S.C. (deposition date: 2012-10-15, release date: 2012-11-21, Last modification date: 2020-07-29)

Primary citation

Schmidt, A.G.,Xu, H.,Khan, A.R.,O'Donnell, T.,Khurana, S.,King, L.R.,Manischewitz, J.,Golding, H.,Suphaphiphat, P.,Carfi, A.,Settembre, E.C.,Dormitzer, P.R.,Kepler, T.B.,Zhang, R.,Moody, M.A.,Haynes, B.F.,Liao, H.X.,Shaw, D.E.,Harrison, S.C.
Preconfiguration of the antigen-binding site during affinity maturation of a broadly neutralizing influenza virus antibody.
Proc.Natl.Acad.Sci.USA, 110:264-269, 2013

PubMed Abstract: Affinity maturation refines a naive B-cell response by selecting mutations in antibody variable domains that enhance antigen binding. We describe a B-cell lineage expressing broadly neutralizing influenza virus antibodies derived from a subject immunized with the 2007 trivalent vaccine. The lineage comprises three mature antibodies, the unmutated common ancestor, and a common intermediate. Their heavy-chain complementarity determining region inserts into the conserved receptor-binding pocket of influenza HA. We show by analysis of structures, binding kinetics and long time-scale molecular dynamics simulations that antibody evolution in this lineage has rigidified the initially flexible heavy-chain complementarity determining region by two nearly independent pathways and that this preconfiguration accounts for most of the affinity gain. The results advance our understanding of strategies for developing more broadly effective influenza vaccines.

PubMed: 23175789
DOI: 10.1073/pnas.1218256109

Experimental method

X-RAY DIFFRACTION (2.5 Å)