Click here to close Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly. We suggest using a current version of Chrome, FireFox, or Safari.
XB-ART-49915
Structure August 6, 2013; 21 (8): 1417-29.

Structure of protein related to Dan and Cerberus: insights into the mechanism of bone morphogenetic protein antagonism.

Nolan K , Kattamuri C , Luedeke DM , Deng X , Jagpal A , Zhang F , Linhardt RJ , Kenny AP , Zorn AM , Thompson TB .


Abstract
The bone morphogenetic proteins (BMPs) are secreted ligands largely known for their functional roles in embryogenesis and tissue development. A number of structurally diverse extracellular antagonists inhibit BMP ligands to regulate signaling. The differential screening-selected gene aberrative in neuroblastoma (DAN) family of antagonists represents the largest group of BMP inhibitors; however, little is known of how they mechanistically inhibit BMP ligands. Here, we present the structure of the DAN family member, protein related to Dan and Cerberus (PRDC), solved by X-ray crystallography. The structure reveals a growth factor-like appearance with an unexpected dimerization mechanism that is formed through extensive β strand contacts. Using site-directed mutagenesis coupled with in vitro and in vivo activity assays, we identified a BMP-binding epitope on PRDC. We also determined that PRDC binds heparin with high affinity and that heparin binding to PRDC interferes with BMP antagonism. These results offer insight for how DAN family antagonists functionally inhibit BMP ligands.

PubMed ID: 23850456
PMC ID: PMC3749838
Article link: Structure
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: cer1 nbl1

References [+] :
Alvarez, Comparative structure analyses of cystine knot-containing molecules with eight aminoacyl ring including glycoprotein hormones (GPH) alpha and beta subunits and GPH-related A2 (GPA2) and B5 (GPB5) molecules. 2009, Pubmed