PDBsum entry 2kd3

Protein binding

PDB id: 2kd3

Contents

Protein chain

97 a.a. *

* Residue conservation analysis

PDB id:

2kd3

Name:

Protein binding

Title:

Nmr structure of the wnt modulator protein sclerostin

Structure:

Sclerostin. Chain: a. Fragment: msost deltanc, unp residues 59-167. Synonym: wnt modulator protein. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

15 models

Authors:

S.E.Weidauer,T.D.Mueller

Key ref:

S.E.Weidauer et al. (2009). NMR structure of the Wnt modulator protein Sclerostin. Biochem Biophys Res Commun, 380, 160-165. PubMed id: 19166819

Date:

02-Jan-09 Release date: 10-Feb-09

Protein chain

Q99P68  (SOST_MOUSE) -  Sclerostin from Mus musculus

Seq: 211 a.a.

Struc: 97 a.a.

Biochem Biophys Res Commun 380:160-165 (2009)

PubMed id: 19166819

NMR structure of the Wnt modulator protein Sclerostin.

S.E.Weidauer, P.Schmieder, M.Beerbaum, W.Schmitz, H.Oschkinat, T.D.Mueller.

ABSTRACT

Sclerostin has been identified as a negative regulator of bone growth. Initially it was considered that Sclerostin performs its regulatory function via acting as a modulator of bone morphogenetic proteins (BMPs) similar to known examples such as Noggin, Chordin, and members of the DAN family. Recent findings, however, show that Sclerostin interferes with the Wnt signaling pathway due to binding to the Wnt co-receptor LRP5 thereby modulating bone growth. As Sclerostin is exclusively produced by osteocytes located in bones, neutralization of its bone-inhibiting functions makes it a highly interesting target for an osteoanabolic therapeutic approach in diseases characterized by bone loss, such as osteoporosis. Despite the huge interest in Sclerostin inhibitors the molecular basis of its function and its interaction with components of the Wnt signaling cascade has remained unclear. Here, we present the NMR structure of murine Sclerostin providing the first insights how Sclerostin might bind to LRP5.