4jph

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

spinqualitylabelsall models 4jph, resolution 2.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4jph is a 4 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CIT, GOL, GSH Gene: Grem2, Cktsf1b2, Prdc (Mus musculus) Resources: FirstGlance, OCA, RCSB, PDBsum Function [GREM2_MOUSE] Cytokine that inhibits the activity of BMP2 and BMP4 in a dose-dependent manner. Antagonized BMP4-induced suppression of progesterone production in granulosa cells. Publication Abstract from PubMed 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 beta 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. 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 Structure. 2013 Jul 9. pii: S0969-2126(13)00206-2. doi:, 10.1016/j.str.2013.06.005. PMID:23850456 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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