4FQR

Crystal structure of broadly neutralizing antibody C05 bound to H3 influenza hemagglutinin

This is a non-PDB format compatible entry.

Summary for 4FQR

• Entry DOI: 10.2210/pdb4fqr/pdb
• Related: 4FNK 4FNL 4FP8
• EMDB information: 2138 2139 2140
• Descriptor: Hemagglutinin HA1 chain, Hemagglutinin HA2 chain, Broadly neutralizing antibody C05, heavy chain, ... (7 entities in total)
• Functional Keywords: viral fusion protein, immunoglobulin, virus attachment and entry, immune recognition, viral protein-immune system complex, viral protein/immune system
• Biological source: Influenza A virus; More
• Total number of polymer chains: 48
• Total formula weight: 1273386.96

Authors

Ekiert, D.C.,Wilson, I.A. (deposition date: 2012-06-25, release date: 2012-09-19, Last modification date: 2024-11-06)

Primary citation

Ekiert, D.C.,Kashyap, A.K.,Steel, J.,Rubrum, A.,Bhabha, G.,Khayat, R.,Lee, J.H.,Dillon, M.A.,O'Neil, R.E.,Faynboym, A.M.,Horowitz, M.,Horowitz, L.,Ward, A.B.,Palese, P.,Webby, R.,Lerner, R.A.,Bhatt, R.R.,Wilson, I.A.
Cross-neutralization of influenza A viruses mediated by a single antibody loop.
Nature, 489:526-532, 2012

PubMed Abstract: Immune recognition of protein antigens relies on the combined interaction of multiple antibody loops, which provide a fairly large footprint and constrain the size and shape of protein surfaces that can be targeted. Single protein loops can mediate extremely high-affinity binding, but it is unclear whether such a mechanism is available to antibodies. Here we report the isolation and characterization of an antibody called C05, which neutralizes strains from multiple subtypes of influenza A virus, including H1, H2 and H3. X-ray and electron microscopy structures show that C05 recognizes conserved elements of the receptor-binding site on the haemagglutinin surface glycoprotein. Recognition of the haemagglutinin receptor-binding site is dominated by a single heavy-chain complementarity-determining region 3 loop, with minor contacts from heavy-chain complementarity-determining region 1, and is sufficient to achieve nanomolar binding with a minimal footprint. Thus, binding predominantly with a single loop can allow antibodies to target small, conserved functional sites on otherwise hypervariable antigens.

PubMed: 22982990
DOI: 10.1038/nature11414

Experimental method

X-RAY DIFFRACTION (4.1 Å)