title: Structure of the apo anti-influenza CH65 Fab.
abstract: Influenza viruses remain a persistent challenge to human health owing to their inherent ability to evade the immune response by antigenic drift. However, the discovery of broadly neutralizing antibodies (bnAbs) against divergent viruses has sparked renewed interest in a universal influenza vaccine and novel therapeutic opportunities. Here, a crystal structure at 1.70 Å resolution is presented of the Fab of the human antibody CH65, which has broad neutralizing activity against a range of seasonal H1 isolates. Previous studies proposed that affinity maturation of this antibody lineage pre-organizes the complementarity-determining region (CDR) loops into an energetically favorable HA-bound conformation. Indeed, from the structural comparisons of free and HA-bound CH65 presented here, the CDR loops, and in particular the heavy-chain CDR3, adopt the same conformations in the free and bound forms. Thus, these findings support the notion that affinity maturation of the CH65 lineage favorably preconfigures the CDR loops for high-affinity binding to influenza hemagglutinin.
authors: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors: Peter S
authors: PS
authors: Lee
authors: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors: Ashley J
authors: AJ
authors: Arnell
authors: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors: Ian A
authors: IA
authors: Wilson
mesh_terms: D057134:Antibodies, Neutralizing / Q000737:chemistry*; D001059:Apoproteins / Q000737:chemistry*; D018360:Crystallography, X-Ray; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry*; D009980:Influenza A virus / Q000276:immunology*; D008958:Models, Molecular; D011485:Protein Binding
chemical_list: D057134:Antibodies, Neutralizing; D001059:Apoproteins; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007140:Immunoglobulin Fab Fragments
keywords: adaptive immunity; affinity maturation; antibody; influenza