Evidence map›Paper›PMID 29330193›Full record

ArticleThe EMBO journal2018

Structure of the human myostatin precursor and determinants of growth factor latency.

Thomas R Cotton, Gerhard Fischer, Xuelu Wang, Jason C McCoy, Magdalena Czepnik, Thomas B Thompson, Marko Hyvönen

Open access · bronzeAbstract read
In one paragraph

Article in The EMBO journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 1 pooled it
2.9field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

45 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. 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 · 2025
    Article
  12. Yet another twist to the regulation of the TGF-β family ligands.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  13. A divergent two-domain structure of the anti-Müllerian hormone prodomain.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Characterization of the molecular mechanisms that govern anti-Müllerian hormone synthesis and activity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
    Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Thomas R CottonDepartment of Biochemistry, University of Cambridge, Cambridge, UK.ORCID 0000-0001-6709-9218
Gerhard FischerDepartment of Biochemistry, University of Cambridge, Cambridge, UK.ORCID 0000-0001-9861-1528
Xuelu WangDepartment of Biochemistry, University of Cambridge, Cambridge, UK.ORCID 0000-0003-4018-6615
Jason C McCoyDepartment of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, Cincinnati, OH, USA.
Magdalena CzepnikDepartment of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, Cincinnati, OH, USA.
Thomas B ThompsonDepartment of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, Cincinnati, OH, USA.ORCID 0000-0002-7041-5047
Marko HyvönenDepartment of Biochemistry, University of Cambridge, Cambridge, UK mh256@cam.ac.uk.ORCID 0000-0001-8683-4070
University of Cambridge · GBUniversity of Cincinnati · US

Funding

Structure-Function Investigation of DAN-mediated BMP AntagonismR01GM114640 · NIGMS · UNIVERSITY OF CINCINNATI · PI THOMPSON, THOMAS B · 2015 to 2018
$1.7M
NIGMS NIH HHS R01 GM114640
6 · The paper itself

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 determined the structure of unprocessed pro-myostatin and analysed the properties of the protein in its different forms. Crystal structures and SAXS analyses show that pro-myostatin adopts an open, V-shaped structure with a domain-swapped arrangement. The pro-mature complex, after cleavage of the furin site, has significantly reduced activity compared with the mature growth factor and persists as a stable complex that is resistant to the natural antagonist follistatin. The latency appears to be conferred by a number of distinct features that collectively stabilise the interaction of the pro-domains with the mature growth factor, enabling a regulated stepwise activation process, distinct from the prototypical pro-TGF-β1. These results provide a basis for understanding the effect of missense mutations in pro-myostatin and pave the way for the design of novel myostatin inhibitors.

Indexed as

Cell LineCrystallography, X-RayEnzyme ActivationFollistatinHEK293 CellsHumansMuscle, SkeletalMyostatinPolymorphism, GeneticProtein PrecursorsProtein Structure, SecondaryProteolysisTransforming Growth Factor betaFollistatinMSTN protein, humanMyostatinProtein PrecursorsTransforming Growth Factor betaGDF8latencymyostatinpro‐domainTGF‐β superfamily

Identifiers

PMID29330193
PMCPMC5793801
OpenAlexW2697458340

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.