9x3y: Difference between revisions

Line 1:

~~'''Unreleased structure'''~~

The ~~entry 9x3y~~ is ~~ON HOLD until 2027~~-10-09

==NPFF bound Mas1 Receptor==

== Structural highlights ==

<table><tr><td colspan='2'>[[9x3y]] is a 2 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=9X3Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9X3Y 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]] 2.77Å</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=9x3y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9x3y OCA], [https://pdbe.org/9x3y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9x3y RCSB], [https://www.ebi.ac.uk/pdbsum/9x3y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9x3y ProSAT]</span></td></tr>

</table>

== Function ==

[https://www.uniprot.org/uniprot/MAS_HUMAN MAS_HUMAN] Receptor for angiotensin 1-7 (By similarity). Acts specifically as a functional antagonist of AGTR1 (angiotensin-2 type 1 receptor), although it up-regulates AGTR1 receptor levels (PubMed:15809376, PubMed:16611642). Positive regulation of AGTR1 levels occurs through activation of the G-proteins GNA11 and GNAQ, and stimulation of the protein kinase C signaling cascade (PubMed:15809376, PubMed:16611642). The antagonist effect on AGTR1 function is probably due to AGTR1 being physically altered by MAS1 (PubMed:15809376, PubMed:16611642).[UniProtKB:P30554]<ref>PMID:15809376</ref> <ref>PMID:16611642</ref>

== Publication Abstract from PubMed ==

The Mas1 receptor, an orphan class A G-protein-coupled receptor (GPCR), plays pivotal roles in cardiovascular and anti-inflammatory regulation. Despite its therapeutic relevance, the structural mechanisms underlying Mas1 ligand binding and activation remain poorly understood. Here, we report cryo-EM structures of Mas1 bound to two chemically distinct agonists-neuropeptide FF (NPFF) and synthetic small-molecule AR234958-captured in complex with inhibitory G proteins. These structures reveal a conserved orthosteric binding pocket accommodating both ligands through shared hydrophobic interactions. Unlike many other class A GPCRs that rely on direct W(6.48) toggle switch engagement, Mas1 adopts a non-canonical activation strategy driven by a ligand-induced hydrophobic compression plane involving residues Y248(6.55), L87(2.60), I84(2.57), and L266(7.39) at the bottom of the ligand binding pocket. This mechanism transmits mechanical tension to promote TM6 displacement and G protein coupling. Functional mutagenesis validates this model, identifying two transmembrane helix 6 (TM6) residues, M244(6.51) and F237(6.44), as critical molecular switches. Comparative analyses of Mas1-related receptors, MRGPRX1-X4, reveal conserved features and mechanistic divergence within this subfamily. These findings provide a structural framework for understanding Mas1 pharmacology and rational design of selective therapeutics.

~~Authors~~:

Structural insight into ligand binding and activation of the orphan GPCR Mas1.,Zhang Y, Wang Q, Liu H, Shan H, Gu Y, Yang J, Gao Y, Wu K, Yang D, Xu HE EMBO J. 2026 Mar 30. doi: 10.1038/s44318-026-00764-6. PMID:41912627<ref>PMID:41912627</ref>

~~Description~~:

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

[[Category: ~~Unreleased~~ Structures]]

</div>

== References ==

__TOC__

</StructureSection>

[[Category: Homo sapiens]]

[[Category: Large Structures]]

[[Category: Liu H]]

[[Category: Xu HE]]

[[Category: Zhang YM]]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9x3y is ON HOLD  until 2027-10-09
+==NPFF bound Mas1 Receptor==
+<StructureSection load='9x3y' size='340' side='right'caption='[[9x3y]], [[Resolution|resolution]] 2.77&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9x3y]] is a 2 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=9X3Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9X3Y 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]] 2.77&#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=9x3y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9x3y OCA], [https://pdbe.org/9x3y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9x3y RCSB], [https://www.ebi.ac.uk/pdbsum/9x3y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9x3y ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/MAS_HUMAN MAS_HUMAN] Receptor for angiotensin 1-7 (By similarity). Acts specifically as a functional antagonist of AGTR1 (angiotensin-2 type 1 receptor), although it up-regulates AGTR1 receptor levels (PubMed:15809376, PubMed:16611642). Positive regulation of AGTR1 levels occurs through activation of the G-proteins GNA11 and GNAQ, and stimulation of the protein kinase C signaling cascade (PubMed:15809376, PubMed:16611642). The antagonist effect on AGTR1 function is probably due to AGTR1 being physically altered by MAS1 (PubMed:15809376, PubMed:16611642).[UniProtKB:P30554]<ref>PMID:15809376</ref> <ref>PMID:16611642</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The Mas1 receptor, an orphan class A G-protein-coupled receptor (GPCR), plays pivotal roles in cardiovascular and anti-inflammatory regulation. Despite its therapeutic relevance, the structural mechanisms underlying Mas1 ligand binding and activation remain poorly understood. Here, we report cryo-EM structures of Mas1 bound to two chemically distinct agonists-neuropeptide FF (NPFF) and synthetic small-molecule AR234958-captured in complex with inhibitory G proteins. These structures reveal a conserved orthosteric binding pocket accommodating both ligands through shared hydrophobic interactions. Unlike many other class A GPCRs that rely on direct W(6.48) toggle switch engagement, Mas1 adopts a non-canonical activation strategy driven by a ligand-induced hydrophobic compression plane involving residues Y248(6.55), L87(2.60), I84(2.57), and L266(7.39) at the bottom of the ligand binding pocket. This mechanism transmits mechanical tension to promote TM6 displacement and G protein coupling. Functional mutagenesis validates this model, identifying two transmembrane helix 6 (TM6) residues, M244(6.51) and F237(6.44), as critical molecular switches. Comparative analyses of Mas1-related receptors, MRGPRX1-X4, reveal conserved features and mechanistic divergence within this subfamily. These findings provide a structural framework for understanding Mas1 pharmacology and rational design of selective therapeutics.
-Authors:
+Structural insight into ligand binding and activation of the orphan GPCR Mas1.,Zhang Y, Wang Q, Liu H, Shan H, Gu Y, Yang J, Gao Y, Wu K, Yang D, Xu HE EMBO J. 2026 Mar 30. doi: 10.1038/s44318-026-00764-6. PMID:41912627<ref>PMID:41912627</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 9x3y" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Liu H]]
+[[Category: Xu HE]]
+[[Category: Zhang YM]]