Mimicry origins | Nature Chemical Biology


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Access through your institution Buy or subscribe _J. Immunol._ 191, 456–463 (2013) Several autoimmune diseases manifest as a result of molecular mimicry, where completely unrelated


molecules, such as an allergen and a self-peptide, share a common receptor. Methyl α-D-mannopyranoside and a dodecapeptide, DVFYPYPYASGS, can be interchangeably bound by the lectin


concanavalin A and a monoclonal antibody 2D10 as well as by polyclonal sera. For concanavalin A, binding of the two ligands occurs at different sites, so the differences in molecular


recognition of the two ligands are not attributable to their different structures per se. For 2D10, it has been suggested from thermodynamic and _in silico_ studies that 2D10 uses a flexible


binding site that can accommodate both antigens. To test this proposal, Tapryal _et al_. solved the crystal structures of a single-chain variable fragment of 2D10 in an antigen-free state


as well as in complexes with the carbohydrate and dodecapeptide. Surprisingly, they found no overall structural differences in the antibody fragments, suggesting a rigid binding site that


does not change upon antigen binding. The authors also found that the carbohydrate bound the antibody primarily through polar interactions, whereas the peptide bound via different polar


interactions but also by hydrophobic interactions. Therefore, molecular mimicry arises by neither the chemical nature nor the equivalence of the interactions nor with any role for


conformational changes at the antigen-binding site but is achieved via plasticity of the antigen-antibody interactions. This is a preview of subscription content, access via your institution


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about institutional subscriptions * Read our FAQs * Contact customer support Authors * Mirella Bucci View author publications You can also search for this author inPubMed Google Scholar


RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Bucci, M. Mimicry origins. _Nat Chem Biol_ 9, 468 (2013). https://doi.org/10.1038/nchembio.1301 Download


citation * Published: 18 July 2013 * Issue Date: August 2013 * DOI: https://doi.org/10.1038/nchembio.1301 SHARE THIS ARTICLE Anyone you share the following link with will be able to read


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