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-Structure paper
Title | Cross-neutralization of influenza A viruses mediated by a single antibody loop. |
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Journal, issue, pages | Nature, Vol. 489, Issue 7417, Page 526-532, Year 2012 |
Publish date | Sep 27, 2012 |
Authors | Damian C Ekiert / Arun K Kashyap / John Steel / Adam Rubrum / Gira Bhabha / Reza Khayat / Jeong Hyun Lee / Michael A Dillon / Ryann E O'Neil / Aleksandr M Faynboym / Michael Horowitz / Lawrence Horowitz / Andrew B Ward / Peter Palese / Richard Webby / Richard A Lerner / Ramesh R Bhatt / Ian A Wilson / |
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 ...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. |
External links | Nature / PubMed:22982990 / PubMed Central |
Methods | EM (single particle) / X-ray diffraction |
Resolution | 1.901 - 17.0 Å |
Structure data | EMDB-2138: EMDB-2139: EMDB-2140: PDB-4fnk: PDB-4fnl: PDB-4fp8: PDB-4fqr: |
Chemicals | ChemComp-NAG: ChemComp-SO4: ChemComp-GOL: ChemComp-HOH: ChemComp-TRS: ChemComp-ZN: |
Source |
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Keywords | VIRAL PROTEIN / viral fusion protein / virus attachment and entry / IMMUNE SYSTEM / Immunoglobulin / immune recognition / VIRAL PROTEIN/IMMUNE SYSTEM / VIRAL PROTEIN-IMMUNE SYSTEM complex |