Myostatin precursor protein (Pro-myostatin)

The myostatin precursor protein (pro-myostatin or latent myostatin) is the biosynthetic, inactive form of myostatin, a key negative regulator of skeletal muscle mass. Synthesized in muscle tissue, pro-myostatin consists of a signal peptide, prodomain (N-terminus), and mature peptide (C-terminus). It is secreted predominantly as a latent, V-shaped homodimeric complex, with its mature domain non-covalently bound by the prodomain. This latent complex maintains myostatin in an inactive state in the extracellular matrix or serum until sequential proteolytic processing releases the mature myostatin. The prodomain confers latency by stabilizing the interaction and rendering the complex resistant to natural antagonists like follistatin. Targeting pro- and latent myostatin represents an innovative therapeutic approach for treatment of muscle wasting disorders by blocking activation upstream of receptor signaling, enhancing tissue specificity and safety. Monitoring serum or interstitial levels of latent myostatin can serve as a biomarker for disease activity and target engagement. Safety concerns arise from possible effects on non-muscle tissues and redundancy among growth factor receptors.

Other names

Latent myostatinGrowth differentiation factor 8 precursor (Pro-GDF-8)Pro-GDF8Myostatin propeptidePrepro-myostatin

Antibody SRK-015 blocks extracellular proteolytic activation of pro- and latent myostatin, stabilizing the latent conformation and preventing maturation into active myostatin, thus inhibiting signaling and muscle growth suppression. Follistatin binds and inhibits myostatin, but is unable to displace the prodomain from the latent complex. Other inhibitors prevent mature myostatin from binding its receptor or act as ligand traps.