2K8P

Characterisation of the structural features and interactions of sclerostin: molecular insight into a key regulator of Wnt-mediated bone formation

2K8P の概要

• エントリーDOI: 10.2210/pdb2k8p/pdb
• 分子名称: Sclerostin (1 entity in total)
• 機能のキーワード: wnt signalling pathway, bone formation, alternative splicing, glycoprotein, secreted, signaling protein
• 由来する生物種: Homo sapiens (man)
• 細胞内の位置: Secreted (Potential): Q9BQB4
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 21432.33

構造登録者

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. (登録日: 2008-09-18, 公開日: 2009-02-17, 最終更新日: 2022-03-16)

主引用文献

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

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: 19208630
DOI: 10.1074/jbc.M807994200

実験手法

SOLUTION NMR