Month: January 2018

Ryan G. Walker, Jason C. McCoy, Magdalena Czepnik, Melanie J. Mills, Adam Haggd, Kelly L. Walton, Thomas R. Cotton, Marko Hyvönen, Richard T. Lee, Paul Gregorevic, Craig A. Harrison, and Thomas B. Thompson

Proceedings of the National Academy of Sciences of the United States of America, 115 (5) E866-E875, 2018

DOI: 10.1073/pnas.1714622115

Pubmed:29348202

Abstract

Growth/differentiation factor 8 (GDF8), or myostatin, negatively regulates muscle mass. GDF8 is held in a latent state through interactions with its N-terminal prodomain, much like TGF-β. Using a combination of small-angle X-ray scattering and mutagenesis, we characterized the interactions of GDF8 with its prodomain. Our results show that the prodomain:GDF8 complex can exist in a fully latent state and an activated or “triggered” state where the prodomain remains in complex with the mature domain. Continue reading →

Thomas Cotton^, Gerhard Fischer, Xuelu Wang^, Jason McCoy, Magdalena Czepnik, Thomas B. Thompson, Marko Hyvönen

The EMBO Journal (2018) 37: 367-383
DOI: 10.15252/embj.201797883
Pre-publication in BiorXiv, DOI: doi.org/10.1101/153403
PDB coordinates: 5NTU (3D view ), 5NXS (3D view )

Abstract

Myostatin, a key regulator of muscle mass in vertebrates, is biosynthesised as a latent precursor in muscle and is activated by sequential proteolysis of the pro-domain. To investigate the molecular mechanism by which pro-myostatin remains latent, we have solved the structure of unprocessed pro-myostatin and analysed the properties of the protein in its different forms. Continue reading →