GDF-11 is the closest paralog of myostatin (GDF-8) - 90% sequence identity in the mature domain. GDF-11 selectivity is the key counter-screen for myostatin inhibitor design: a peptide that blocks GDF-8 but not GDF-11 avoids potential off-target effects on neurogenesis and cardiac development.
The GDF-8 vs GDF-11 selectivity question is scientifically controversial (Egerman et al. 2015 vs Sinha et al. 2014). Platform cards track off_target_delta_gdf11 as a standard metric.
GDF-11 is a TGF-β superfamily member that shares ~90% mature-domain sequence identity with myostatin (GDF-8) and uses the same ACVR2B/ALK4/5/7 receptor complex - making it structurally and functionally intertwined with the muscle atrophy and aging axes. It is essential for embryonic anterior-posterior patterning, kidney development, and pancreatic/olfactory morphogenesis. In adults, GDF-11 influences erythropoiesis, cardiac mass, and neural progenitor activity. The controversy over whether circulating GDF-11 declines with age and drives tissue aging (the "rejuvenating factor" debate) remains unresolved and continues to generate preclinical research. Every scaffold targeting the ActRII axis for anti-aging or muscle-building intersects this card.
GDF11 (chromosome 12q13.2, 4 exons) encodes a 407-aa precursor. Signal peptide cleavage and prodomain removal yield the mature ~12.5 kDa monomer, which homodimerizes via cystine-knot into a 25 kDa active dimer. The crystal structure (1.50 Å) reveals the canonical TGF-β hand-like fold: cystine-knot palm, finger-like β-strands, an α-helical wrist for type II receptor engagement, and a knuckle epitope for type I receptor recruitment. GDF-11 binds ACVR2B > ACVR2A, then recruits ALK4, ALK5, or ALK7 (the ALK5 engagement distinguishes GDF-11 from GDF-8, which has reduced ALK7 affinity) → Smad2/3 phosphorylation → Smad4 nuclear complex → cell cycle inhibition (p15/CDKN2B), Id1/Id2 repression, and differentiation gene programs. Non-canonical signaling includes MAPK/ERK and PI3K/Akt in neural contexts. Follistatin and GASP-1 neutralize GDF-11. The prodomain maintains latency until BMP1/tolloid proteolysis. GDF-11 and GDF-8 are nearly indistinguishable by many antibodies - a key source of the aging controversy.
No approved drug targets GDF-11 specifically. Luspatercept (ACE-536) traps GDF-11 along with activins to promote erythropoiesis and is FDA-approved for MDS anemia and beta-thalassemia. Anti-GDF-11 effects are embedded in pan-ActRII trap results. For peptide research, the tractable recipes are: GDF-11 prodomain-mimetic peptides that maintain ligand latency and suppress local GDF-11 activity in specific tissue compartments (e.g., heart, muscle) without pan-ActRII blockade; follistatin domain fragments that selectively bind GDF-11 over activin A to tease apart their independent contributions to erythropoiesis suppression; and GDF-11/GDF-8 chimeric mature-domain peptides that probe the structural basis for differential ALK7 engagement and separate the developmental patterning function from the muscle/metabolic one. The GDF-11 vs. GDF-8 subtype distinction is the critical fork for any scaffold aimed at muscle mass without perturbing embryonic or erythroid biology.
VNDNTLFKWMIFNG · 14 aa · @peptidemodel
| # | id | title | author | status | refs | ipSAE_d0chn | ♥ |
|---|---|---|---|---|---|---|---|
| 1 | pep-10794 | BSK1-2 aging-research peptide fragment | pe@peptidemodel | 2 | — | 0 | |
| 2 | pep-10791 | Muscle-growth booster peptide: follistatin fragment (1-27) | pe@peptidemodel | 1 | — | 0 |
No discussion threads yet.