ArticleProceedings of the National Academy of Sciences of the United States of America2018
Molecular characterization of latent GDF8 reveals mechanisms of activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
26 citing papers in PubMed, 36 citations in OpenAlex.
- Activated GDF11/8 subforms predict cardiovascular events and mortality in humans.Nature communications · 2025Article
- Prodomain processing controls BMP-10 bioactivity and targeting to fibrillin-1 in latent conformation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- A divergent two-domain structure of the anti-Müllerian hormone prodomain.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Omics-driven investigation of the biology underlying intrinsic submaximal working capacity and its trainability.Physiological genomics · 2023Article
- GDF11 and aging biology - controversies resolved and pending.The journal of cardiovascular aging · 2023Article
- Inhibitor Design Strategy for Myostatin: Dynamics and Interaction Networks Define the Affinity and Release Mechanisms of the Inhibited Complexes.Molecules (Basel, Switzerland) · 2023Article
- Increasing Skeletal Muscle Mass in Mice by Non-Invasive Intramuscular Delivery of Myostatin Inhibitory Peptide by Iontophoresis.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Protection of the Prodomain α1-Helix Correlates with Latency in the Transforming Growth Factor-β Family.Journal of molecular biology · 2022Article
- Myostatin/Activin Receptor Ligands in Muscle and the Development Status of Attenuating Drugs.Endocrine reviews · 2022Review
- Review
- Characterization of tolloid-mediated cleavage of the GDF8 procomplex.The Biochemical journal · 2021Article
- Review
- Similar sequences but dissimilar biological functions of GDF11 and myostatin.Experimental & molecular medicine · 2020Review
- Mutational Analysis of the Putative Anti-Müllerian Hormone (AMH) Binding Interface on its Type II Receptor, AMHR2.Endocrinology · 2020Article
- Structural basis of specific inhibition of extracellular activation of pro- or latent myostatin by the monoclonal antibody SRK-015.The Journal of biological chemistry · 2020Article
- GDF11 promotes osteogenesis as opposed to MSTN, and follistatin, a MSTN/GDF11 inhibitor, increases muscle mass but weakens bone.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Article
- Variation in zygotic CRISPR/Cas9 gene editing outcomes generates novel reporter and deletion alleles at the Gdf11 locus.Scientific reports · 2019Article
- Specification of BMP Signaling.Cells · 2019Review
- Structural biology of the TGFβ family.Experimental biology and medicine (Maywood, N.J.) · 2019Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
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. However, these states are not reversible, indicating the latent GDF8 is "spring-loaded." Structural analysis shows that the prodomain:GDF8 complex adopts an "open" configuration, distinct from the latency state of TGF-β and more similar to the open state of Activin A and BMP9 (nonlatent complexes). We determined that GDF8 maintains similar features for latency, including the alpha-1 helix and fastener elements, and identified a series of mutations in the prodomain of GDF8 that alleviate latency, including I56E, which does not require activation by the protease Tolloid. In vivo, active GDF8 variants were potent negative regulators of muscle mass, compared with WT GDF8. Collectively, these results help characterize the latency and activation mechanisms of GDF8.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.