5NTU
Crystal Structure of human Pro-myostatin Precursor at 2.6 A Resolution
Summary for 5NTU
| Entry DOI | 10.2210/pdb5ntu/pdb |
| Descriptor | Growth/differentiation factor 8, CHLORIDE ION, 1,2-ETHANEDIOL, ... (4 entities in total) |
| Functional Keywords | growth factor, signalling protein, tgfbeta family, cystine knot, signaling protein |
| Biological source | Homo sapiens (Human) |
| Cellular location | Secreted : O14793 |
| Total number of polymer chains | 2 |
| Total formula weight | 77136.99 |
| Authors | Cotton, T.R.,Fischer, G.,Hyvonen, M. (deposition date: 2017-04-28, release date: 2018-01-17, Last modification date: 2024-11-13) |
| Primary citation | Cotton, T.R.,Fischer, G.,Wang, X.,McCoy, J.C.,Czepnik, M.,Thompson, T.B.,Hyvonen, M. Structure of the human myostatin precursor and determinants of growth factor latency. EMBO J., 37:367-383, 2018 Cited by PubMed 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. PubMed: 29330193DOI: 10.15252/embj.201797883 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.58 Å) |
Structure validation
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