View source for 9fdy


==Betaglycan Orphan Domain (ratBGo) in complex with TGF-b1 and extracellular domain of TGFBRII==
<StructureSection load='9fdy' size='340' side='right'caption='[[9fdy]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9fdy]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9FDY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9FDY FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.4&#8491;</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=9fdy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9fdy OCA], [https://pdbe.org/9fdy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9fdy RCSB], [https://www.ebi.ac.uk/pdbsum/9fdy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9fdy ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/TGFB1_HUMAN TGFB1_HUMAN] Defects in TGFB1 are the cause of Camurati-Engelmann disease (CE) [MIM:[https://omim.org/entry/131300 131300]; also known as progressive diaphyseal dysplasia 1 (DPD1). CE is an autosomal dominant disorder characterized by hyperostosis and sclerosis of the diaphyses of long bones. The disease typically presents in early childhood with pain, muscular weakness and waddling gait, and in some cases other features such as exophthalmos, facial paralysis, hearing difficulties and loss of vision.<ref>PMID:10973241</ref> <ref>PMID:11062463</ref> <ref>PMID:12493741</ref> <ref>PMID:12843182</ref> <ref>PMID:15103729</ref> 
== Function ==
[https://www.uniprot.org/uniprot/TGFB1_HUMAN TGFB1_HUMAN] Multifunctional protein that controls proliferation, differentiation and other functions in many cell types. Many cells synthesize TGFB1 and have specific receptors for it. It positively and negatively regulates many other growth factors. It plays an important role in bone remodeling as it is a potent stimulator of osteoblastic bone formation, causing chemotaxis, proliferation and differentiation in committed osteoblasts.
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== Publication Abstract from PubMed ==
Betaglycan (BG) is a transmembrane co-receptor of the transforming growth factor-beta (TGF-beta) family of signaling ligands. It is essential for embryonic development, tissue homeostasis and fertility in adults. It functions by enabling binding of the three TGF-beta isoforms to their signaling receptors and is additionally required for inhibin A (InhA) activity. Despite its requirement for the functions of TGF-betas and InhA in vivo, structural information explaining BG ligand selectivity and its mechanism of action is lacking. Here, we determine the structure of TGF-beta bound both to BG and the signaling receptors, TGFBR1 and TGFBR2. We identify key regions responsible for ligand engagement, which has revealed binding interfaces that differ from those described for the closely related co-receptor of the TGF-beta family, endoglin, thus demonstrating remarkable evolutionary adaptation to enable ligand selectivity. Finally, we provide a structural explanation for the hand-off mechanism underlying TGF-beta signal potentiation.

Structures of TGF-beta with betaglycan and signaling receptors reveal mechanisms of complex assembly and signaling.,Wieteska L, Taylor AB, Punch E, Coleman JA, Conway IO, Lin YF, Byeon CH, Hinck CS, Krzysiak T, Ishima R, Lopez-Casillas F, Cherepanov P, Bernard DJ, Hill CS, Hinck AP Nat Commun. 2025 Feb 26;16(1):1778. doi: 10.1038/s41467-025-56796-9. PMID:40011426<ref>PMID:40011426</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 9fdy" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Cherepanov P]]
[[Category: Hill CS]]
[[Category: Hinck AP]]
[[Category: Punch E]]
[[Category: Wieteska L]]