4WUK

Crystal structure of apo CH65 Fab

Summary for 4WUK

• Entry DOI: 10.2210/pdb4wuk/pdb
• Descriptor: CH65 heavy chain, CH65 light chain, 2-[N-CYCLOHEXYLAMINO]ETHANE SULFONIC ACID, ... (4 entities in total)
• Functional Keywords: immunoglobulin, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 2
• Total formula weight: 48540.98

Authors

Lee, P.S.,Wilson, I.A. (deposition date: 2014-11-01, release date: 2015-02-25, Last modification date: 2024-10-23)

Primary citation

Lee, P.S.,Arnell, A.J.,Wilson, I.A.
Structure of the apo anti-influenza CH65 Fab.
Acta Crystallogr.,Sect.F, 71:145-148, 2015

PubMed 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.

PubMed: 25664786
DOI: 10.1107/S2053230X14027599

Experimental method

X-RAY DIFFRACTION (1.7 Å)