View source for 9dpu


==BMP-9 G389S Dimer in Acidic pH==
<StructureSection load='9dpu' size='340' side='right'caption='[[9dpu]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9dpu]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9DPU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9DPU FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></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=9dpu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9dpu OCA], [https://pdbe.org/9dpu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9dpu RCSB], [https://www.ebi.ac.uk/pdbsum/9dpu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9dpu ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GDF2_HUMAN GDF2_HUMAN] Potent circulating inhibitor of angiogenesis. Could be involved in bone formation. Signals through the type I activin receptor ACVRL1 but not other Alks.<ref>PMID:18309101</ref> <ref>PMID:22799562</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
BMP-9 and BMP-10 are TGF-beta family signaling ligands naturally secreted into blood. They act on endothelial cells and are required for proper development and maintenance of the vasculature. In hereditary hemorrhagic telangiectasia, regulation is disrupted due to mutations in the BMP-9/10 pathway, namely in the type I receptor ALK1 or the co-receptor endoglin. It has been demonstrated that BMP-9/10 heterodimers are the most abundant signaling species in the blood, but it is unclear how they form. Unlike other ligands of the TGF-beta family, BMP-9 and -10 are secreted as a mixture of disulfide-linked dimers and monomers in which the interchain cysteine (Cys-392) remains either unpaired or paired. Here, we show that the monomers are secreted in a cysteinylated form that crystallizes as a non-covalent dimer. Despite this, monomers do not self-associate at micromolar or lower concentrations and have reduced signaling potency compared to disulfide-linked dimers. We further show using protein crystallography that the interchain disulfide of the BMP-9 homodimer adopts a highly strained syn-periplanar conformation. Hence, geometric strain across the interchain disulfide is responsible for infrequent interchain disulfide bond formation, not the cysteinylation. Additionally, we show that interchain disulfide bond formation occurs less in BMP-9 than BMP-10 and these frequencies can be reversed by swapping residues near the interchain disulfide that form attractive interactions with the opposing protomer. Finally, we discuss the implications of these observations on BMP-9/10 heterodimer formation.

Molecular basis of interchain disulfide bond formation in BMP-9 and BMP-10.,Schwartze TA, Morosky SA, Rosato TL, Henrickson A, Lin G, Hinck CS, Taylor AB, Olsen SK, Calero G, Demeler B, Roman BL, Hinck AP J Mol Biol. 2025 Jan 8:168935. doi: 10.1016/j.jmb.2025.168935. PMID:39793884<ref>PMID:39793884</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9dpu" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Hinck AP]]
[[Category: Schwartze TA]]