2K8P
Characterisation of the structural features and interactions of sclerostin: molecular insight into a key regulator of Wnt-mediated bone formation
Summary for 2K8P
| Entry DOI | 10.2210/pdb2k8p/pdb |
| Descriptor | Sclerostin (1 entity in total) |
| Functional Keywords | wnt signalling pathway, bone formation, alternative splicing, glycoprotein, secreted, signaling protein |
| Biological source | Homo sapiens (man) |
| Cellular location | Secreted (Potential): Q9BQB4 |
| Total number of polymer chains | 1 |
| Total formula weight | 21432.33 |
| Authors | Veverka, V.,Henry, A.J.,Slocombe, P.M.,Ventom, A.,Mulloy, B.,Muskett, F.W.,Muzylak, M.,Greenslade, K.,Moore, A.,Zhang, L.,Gong, J.,Qian, X.,Paszty, C.,Taylor, R.J.,Robinson, M.K.,Carr, M.D. (deposition date: 2008-09-18, release date: 2009-02-17, Last modification date: 2024-11-06) |
| Primary citation | Veverka, V.,Henry, A.J.,Slocombe, P.M.,Ventom, A.,Mulloy, B.,Muskett, F.W.,Muzylak, M.,Greenslade, K.,Moore, A.,Zhang, L.,Gong, J.,Qian, X.,Paszty, C.,Taylor, R.J.,Robinson, M.K.,Carr, M.D. Characterization of the Structural Features and Interactions of Sclerostin: Molecular insight into a key regulator of Wnt-mediated bone formation J.Biol.Chem., 284:10890-10900, 2009 Cited by PubMed Abstract: The secreted glycoprotein sclerostin has recently emerged as a key negative regulator of Wnt signaling in bone and has stimulated considerable interest as a potential target for therapeutics designed to treat conditions associated with low bone mass, such as osteoporosis. We have determined the structure of sclerostin, which resulted in the identification of a previously unknown binding site for heparin, suggestive of a functional role in localizing sclerostin to the surface of target cells. We have also mapped the interaction site for an antibody that blocks the inhibition of Wnt signaling by sclerostin. This shows minimal overlap with the heparin binding site and highlights a key role for this region of sclerostin in protein interactions associated with the inhibition of Wnt signaling. The conserved N- and C-terminal arms of sclerostin were found to be unstructured, highly flexible, and unaffected by heparin binding, which suggests a role in stabilizing interactions with target proteins. PubMed: 19208630DOI: 10.1074/jbc.M807994200 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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