4JPH

Crystal structure of Protein Related to DAN and Cerberus (PRDC)

Summary for 4JPH

• Entry DOI: 10.2210/pdb4jph/pdb
• Descriptor: Gremlin-2, GLYCEROL, GLUTATHIONE, ... (5 entities in total)
• Functional Keywords: cystine knot, dan domain, can domain, bmp antagonist, bmp-2, bmp-4, bmp-7, gdf-5, gsh, extracellular, cytokine
• Biological source: Mus musculus (mouse)
• Cellular location: Secreted : O88273
• Total number of polymer chains: 4
• Total formula weight: 71273.38

Authors

Deng, X.,Nolan, K.T.,Kattamuri, C.,Thompson, T.B. (deposition date: 2013-03-19, release date: 2013-07-24, Last modification date: 2025-03-26)

Primary citation

Nolan, K.,Kattamuri, C.,Luedeke, D.M.,Deng, X.,Jagpal, A.,Zhang, F.,Linhardt, R.J.,Kenny, A.P.,Zorn, A.M.,Thompson, T.B.
Structure of protein related to dan and cerberus: insights into the mechanism of bone morphogenetic protein antagonism.
Structure, 21:1417-1429, 2013

PubMed 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: 23850456
DOI: 10.1016/j.str.2013.06.005

Experimental method

X-RAY DIFFRACTION (2.25 Å)