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Biological Chemistry

How Antibodies Assemble To Activate The Immune Response

Six immunoglobulin G antibodies rally around an antigen to spur immune system to fight invaders

by Sarah Everts
March 17, 2014 | APPEARED IN VOLUME 92, ISSUE 11

ANTIBODY ARCHITECTURE
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Credit: Joost Bakker/
www.scicomvisuals.com
To get the immune system to take on invaders, six immunoglobulin G antibodies assemble into a hexagon.
09211-scicon-diebolder1HRcxd.jpg
Credit: Joost Bakker/
www.scicomvisuals.com
To get the immune system to take on invaders, six immunoglobulin G antibodies assemble into a hexagon.

Our immune systems spring into action when antibodies detect the antigens of pathogenic invaders. But it’s remained unclear exactly how these antibodies—known as immunoglobulin G (IgG)—arrange around antigens to kick-start the fight against these pathogens. An international team of structural biologists has finally provided a glimpse of the architecture of these IgG antibody assemblies (Science 2014, DOI: 10.1126/science.1248943). Using electron microscopy, X-ray crystallography, and computer modeling, Piet Gros of Utrecht University, in the Netherlands; Paul W. H. I. Parren of the Danish biotech company Genmab; and colleagues show that six IgG antibodies form a symmetrical hexamer around an antigen on the membrane of a pathogenic cell. They report that mutating amino acid residues at the interface of these six antibodies can enhance or impede the hexamer’s assembly. The team argues that understanding the basis of this hexamerization should help researchers engineer therapeutic antibodies with enhanced abilities to stimulate the immune system.

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