9bao

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Current revision (06:22, 29 January 2025) (edit) (undo)
 
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'''Unreleased structure'''
 
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The entry 9bao is ON HOLD until Paper Publication
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==The Anti-Mullerian Hormone prodomain in complex with the growth factor and 6E11 Fab in C2 symmetry==
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<StructureSection load='9bao' size='340' side='right'caption='[[9bao]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[9bao]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9BAO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9BAO FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.2&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9bao FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9bao OCA], [https://pdbe.org/9bao PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9bao RCSB], [https://www.ebi.ac.uk/pdbsum/9bao PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9bao ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/MIS_HUMAN MIS_HUMAN] Persistent Muellerian duct syndrome. The disease is caused by variants affecting the gene represented in this entry.
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== Function ==
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[https://www.uniprot.org/uniprot/MIS_HUMAN MIS_HUMAN] Plays an important role in several reproductive functions. Induces Muellerian duct regression during male fetal sexual differentiation (PubMed:34155118, PubMed:3754790, PubMed:8469238). Also plays a role in Leydig cell differentiation and function (By similarity). In female acts as a negative regulator of the primordial to primary follicle transition and decreases FSH sensitivity of growing follicles (PubMed:14742691). AMH signals by binding to a specific type-II receptor, AMHR2, that heterodimerizes with type-I receptors (ACVR1 and BMPR1A), and recruiting SMAD proteins that are translocated to the nucleus to regulate target gene expression (PubMed:20861221, PubMed:34155118).[UniProtKB:P27106]<ref>PMID:14742691</ref> <ref>PMID:20861221</ref> <ref>PMID:34155118</ref> <ref>PMID:3754790</ref> <ref>PMID:8469238</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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TGFbeta family ligands are synthesized as precursors consisting of an N-terminal prodomain and C-terminal growth factor (GF) signaling domain. After proteolytic processing, the prodomain typically remains noncovalently associated with the GF, sometimes forming a high-affinity latent procomplex that requires activation. For the TGFbeta family ligand anti-Mullerian hormone (AMH), the prodomain maintains a high-affinity interaction with its GF that does not render it latent. While the prodomain can be displaced by the type II receptor, AMHR2, the nature of the GF:prodomain interaction and the mechanism of prodomain displacement by AMHR2 are currently unknown. We show here that the AMH prodomain exhibits an atypical two-domain structure, containing a dimerizing and a GF-binding domain connected through a flexible linker. Cryo-EM and genomic analyses show that the distinctive GF-binding domain, the result of an exon insertion 450 Mya, comprises a helical bundle and a belt-like structure which interact with the GF at the type II and I receptor binding sites, respectively. The dimerizing domain, which adopts a TGFbeta-like propeptide fold, covalently connects two prodomains through intermolecular disulfide bonds. Disease mutations map to both the GF-binding and dimerization domains. Our results support a model where AMHR2 displaces the helical bundle and induces a conformational change in the GF, followed by release of the prodomain and engagement of the type I receptor. Collectively, this study shows that the AMH prodomain has evolved an atypical binding interaction with the GF that favors, without disrupting signaling, the maintenance of a noncovalent complex until receptors are engaged.
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Authors: Howard, J.A., Thompson, T.B.
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A divergent two-domain structure of the anti-Mullerian hormone prodomain.,Howard JA, Hok L, Cate RL, Sanford NJ, Hart KN, Leach EAE, Bruening AS, Nagykery N, Donahoe PK, Pepin D, Thompson TB Proc Natl Acad Sci U S A. 2025 Jan 21;122(3):e2418088122. doi: , 10.1073/pnas.2418088122. Epub 2025 Jan 13. PMID:39805014<ref>PMID:39805014</ref>
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Description: The Anti-Mullerian Hormone prodomain in complex with the growth factor and 6E11 Fab in C2 symmetry
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Thompson, T.B]]
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<div class="pdbe-citations 9bao" style="background-color:#fffaf0;"></div>
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[[Category: Howard, J.A]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Mus musculus]]
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[[Category: Howard JA]]
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[[Category: Thompson TB]]

Current revision

The Anti-Mullerian Hormone prodomain in complex with the growth factor and 6E11 Fab in C2 symmetry

PDB ID 9bao

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