4jph: Difference between revisions

Latest revision as of 22:59, 26 March 2025

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

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.
Method:	X-ray diffraction, Resolution 2.25Å
Ligands:	CIT, GOL, GSH
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.^[1]

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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Sudo S, Avsian-Kretchmer O, Wang LS, Hsueh AJ. Protein related to DAN and cerberus is a bone morphogenetic protein antagonist that participates in ovarian paracrine regulation. J Biol Chem. 2004 May 28;279(22):23134-41. Epub 2004 Mar 23. PMID:15039429 doi:10.1074/jbc.M402376200
↑ Nolan K, Kattamuri C, Luedeke DM, Deng X, Jagpal A, Zhang F, Linhardt RJ, Kenny AP, Zorn AM, Thompson TB. Structure of Protein Related to Dan and Cerberus: Insights into the Mechanism of Bone Morphogenetic Protein Antagonism. Structure. 2013 Jul 9. pii: S0969-2126(13)00206-2. doi:, 10.1016/j.str.2013.06.005. PMID:23850456 doi:10.1016/j.str.2013.06.005

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OCA

[1] Sudo S, Avsian-Kretchmer O, Wang LS, Hsueh AJ. Protein related to DAN and cerberus is a bone morphogenetic protein antagonist that participates in ovarian paracrine regulation. J Biol Chem. 2004 May 28;279(22):23134-41. Epub 2004 Mar 23. PMID:15039429 doi:10.1074/jbc.M402376200

[2] Nolan K, Kattamuri C, Luedeke DM, Deng X, Jagpal A, Zhang F, Linhardt RJ, Kenny AP, Zorn AM, Thompson TB. Structure of Protein Related to Dan and Cerberus: Insights into the Mechanism of Bone Morphogenetic Protein Antagonism. Structure. 2013 Jul 9. pii: S0969-2126(13)00206-2. doi:, 10.1016/j.str.2013.06.005. PMID:23850456 doi:10.1016/j.str.2013.06.005

[1]

[2]

@@ Line 1: / Line 1: @@
 ==Crystal structure of Protein Related to DAN and Cerberus (PRDC)==
-<StructureSection load='4jph' size='340' side='right' caption='[[4jph]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
+<StructureSection load='4jph' size='340' side='right'caption='[[4jph]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4jph]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JPH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JPH FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4jph]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JPH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JPH FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.25&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Grem2, Cktsf1b2, Prdc ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4jph FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jph OCA], [http://pdbe.org/4jph PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4jph RCSB], [http://www.ebi.ac.uk/pdbsum/4jph PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4jph ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4jph FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jph OCA], [https://pdbe.org/4jph PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jph RCSB], [https://www.ebi.ac.uk/pdbsum/4jph PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jph ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/GREM2_MOUSE 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.<ref>PMID:15039429</ref>
+[https://www.uniprot.org/uniprot/GREM2_MOUSE 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.<ref>PMID:15039429</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Lk3 transgenic mice]]
+[[Category: Large Structures]]
-[[Category: Deng, X]]
+[[Category: Mus musculus]]
-[[Category: Kattamuri, C]]
+[[Category: Deng X]]
-[[Category: Nolan, K T]]
+[[Category: Kattamuri C]]
-[[Category: Thompson, T B]]
+[[Category: Nolan KT]]
-[[Category: Bmp antagonist]]
+[[Category: Thompson TB]]
-[[Category: Bmp-2]]
-[[Category: Bmp-4]]
-[[Category: Bmp-7]]
-[[Category: Can domain]]
-[[Category: Cystine knot]]
-[[Category: Cytokine]]
-[[Category: Dan domain]]
-[[Category: Extracellular]]
-[[Category: Gdf-5]]
-[[Category: Gsh]]

4jph: Difference between revisions

Latest revision as of 22:59, 26 March 2025

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

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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