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. 2020 Jun 9;9:e54582. doi: 10.7554/eLife.54582

Figure 2. Conceptual framework for designing ‘agonist-only’ Activin A muteins.

Figure 2.

(A) Agonist only Activin A muteins (blue) should retain activation of the Smad2/3 pathway like wild type Activin A (red; left panels), and they should retain ability to be inhibited by the endogenous antagonists Follistatin and FSTL3 (grey; right panels). (B) As a result of a loss of ACVR1 binding, Activin A muteins should be less effective inhibitors of BMP-mediated signaling to the Smad1/5/8 pathway. Therefore, we expect that the agonist only muteins should have reduced antagonism of Smad1/5/8 signaling compared to wild-type Activin A. However, antagonism will not be entirely lost, as the agonist-only mutein must still bind to type II receptors for activation of Smad2/3 signaling via ACVR1B (and, to a lesser extent, TGFBR1).