Rxivist logo

Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 67,048 bioRxiv papers from 294,989 authors.

The finger 2 tip loop of Activin A is required for the formation of its non-signaling complex with ACVR1 and type II Bone Morphogenetic Protein receptors

By Vincent Idone, Richard A Corpina, Erich J Goebel, Camille J Cunanan, Alexandra Dimitriou, Hyonjong Kim, Qian Zhang, Ashique Rafique, Raymond Leidich, Xin Wang, Joyce McClain, Andrew J Murphy, Thomas B. Thompson, Aris N Economides

Posted 12 Aug 2019
bioRxiv DOI: 10.1101/733147

Activin A, a ligand that belongs to the BMP/TGFβ family, functions in BMP signaling in two distinctly different ways: it binds to its cognate type II receptors — ACVR2A, ACVR2B, and BMPR2 — and the resulting complex either engages the type I receptor ACVR1B to activate Smad2/3 signaling or binds with the type I receptor ACVR1 to form a non-signaling complex. In order to set the stage for exploring potential biological roles of the non-signaling complex, we engineered Activin A variants that retain their ability to activate ACVR1B but are unable to generate the Activin A · type II receptor · ACVR1 non-signaling complex. This was accomplished by designing Activin A muteins wherein type I-binding regions were replaced with those of Nodal, a BMP/TGFβ family member that utilizes ACVR1B but not ACVR1 as its type I receptor. Of the resulting muteins, an Activin A utilizing the finger 2 tip loop of Nodal (Activin A.Nod.F2TL) fulfilled our specifications; it failed to generate the non-signaling complex, yet activated ACVR1B akin to wild type Activin A. Furthermore, a single amino acid, D406, appears to be a main driver of this interaction, as its deletion results in a mutein that is similar in activity to Activin A.Nod.F2TL. These results define a region of Activin A that is important for the formation of the non-signaling complex and set the stage for engineering knock-in mice where the role of the non-signaling complex can be explored.

Download data

  • Downloaded 114 times
  • Download rankings, all-time:
    • Site-wide: 60,188 out of 67,095
    • In cell biology: 2,934 out of 3,249
  • Year to date:
    • Site-wide: 43,681 out of 67,095
  • Since beginning of last month:
    • Site-wide: 22,279 out of 67,095

Altmetric data

Downloads over time

Distribution of downloads per paper, site-wide

Sign up for the Rxivist weekly newsletter! (Click here for more details.)