AI Article Synopsis
- Agonism of the erythropoietin receptor (EpoR) for red blood cell production has traditionally relied on erythropoietin (EPO), but its short half-life has led to alternative agonists like antibodies.
- Research has focused on how these different agonists activate the EpoR and whether their binding mechanisms are similar to EPO.
- A study using scanning alanine and arginine mutagenesis identified that some antibody constructs bind to the same sites as EPO, while others have unique binding patterns, revealing the extensive range of critical binding regions for signaling in the EpoR.
Article Abstract
Stimulation of red cell production through agonism of the erythropoietin receptor (EpoR) has historically been accomplished through administration of erythropoietin (EPO), the native ligand. The short half-life of EPO has led to the development of a variety of other agonists, including antibodies. It is of considerable interest to understand how these agents might activate the EpoR and whether or not it is important to bind in a manner similar to the native ligand. The binding epitopes of a panel of eight agonistic, single-chain antibody (scFv-Fc) constructs were determined through scanning alanine mutagenesis as well as more limited arginine mutagenesis of the receptor. It was found that while some of these constructs bound to receptor epitopes shared by the ligand, others bound in completely unique ways. The use of a panel of agonists and scanning mutagenesis can define the critical binding regions for signaling; in the case of the EpoR, these regions were remarkably broad.
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| http://dx.doi.org/10.1021/bi1001147 | DOI Listing |
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