9ban: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older edit
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,330,058 edits
No edit summary
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,330,058 edits
No edit summary
 
Line 1: Line 1:
'''Unreleased structure'''


The entry 9ban is ON HOLD  until Paper Publication
==The Anti-Mullerian Hormone prodomain in complex with the growth factor and 6E11 Fab in C1 symmetry==
<StructureSection load='9ban' size='340' side='right'caption='[[9ban]], [[Resolution|resolution]] 3.39&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9ban]] 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=9BAN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9BAN 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]] 3.39&#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=9ban FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9ban OCA], [https://pdbe.org/9ban PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9ban RCSB], [https://www.ebi.ac.uk/pdbsum/9ban PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9ban ProSAT]</span></td></tr>
</table>
== Disease ==
[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.
== Function ==
[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>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.


Authors: Howard, J.A., Thompson, T.B.
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>


Description: The Anti-Mullerian Hormone prodomain in complex with the growth factor and 6E11 Fab in C1 symmetry
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Howard, J.A]]
<div class="pdbe-citations 9ban" style="background-color:#fffaf0;"></div>
[[Category: Thompson, T.B]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Howard JA]]
[[Category: Thompson TB]]
Retrieved from "https://proteopedia.org/9ban"