4JPH

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

4JPH の概要

• エントリーDOI: 10.2210/pdb4jph/pdb
• 分子名称: Gremlin-2, GLYCEROL, GLUTATHIONE, ... (5 entities in total)
• 機能のキーワード: cystine knot, dan domain, can domain, bmp antagonist, bmp-2, bmp-4, bmp-7, gdf-5, gsh, extracellular, cytokine
• 由来する生物種: Mus musculus (mouse)
• 細胞内の位置: Secreted : O88273
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 71273.38

構造登録者

Deng, X.,Nolan, K.T.,Kattamuri, C.,Thompson, T.B. (登録日: 2013-03-19, 公開日: 2013-07-24, 最終更新日: 2025-03-26)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.25 Å)