7sr2: Difference between revisions
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==Crystal structure of the human SNX25 regulator of G-protein signalling (RGS) domain== | ==Crystal structure of the human SNX25 regulator of G-protein signalling (RGS) domain== | ||
<StructureSection load='7sr2' size='340' side='right'caption='[[7sr2]]' scene=''> | <StructureSection load='7sr2' size='340' side='right'caption='[[7sr2]], [[Resolution|resolution]] 2.42Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7SR2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SR2 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7sr2]] 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=7SR2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SR2 FirstGlance]. <br> | ||
</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=7sr2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sr2 OCA], [https://pdbe.org/7sr2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sr2 RCSB], [https://www.ebi.ac.uk/pdbsum/7sr2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sr2 ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.42Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=LEU:LEUCINE'>LEU</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7sr2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sr2 OCA], [https://pdbe.org/7sr2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sr2 RCSB], [https://www.ebi.ac.uk/pdbsum/7sr2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sr2 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/SNX25_HUMAN SNX25_HUMAN] May be involved in several stages of intracellular trafficking. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Recent advances in protein structure prediction using machine learning such as AlphaFold2 and RosettaFold presage a revolution in structural biology. Genome-wide predictions of protein structures are providing unprecedented insights into their architecture and intradomain interactions, and applications have already progressed towards assessing protein complex formation. Here we present detailed analyses of the sorting nexin proteins that contain regulator of G-protein signalling domains (SNX-RGS proteins), providing a key example of the ability of AlphaFold2 to reveal novel structures with previously unsuspected biological functions. These large proteins are conserved in most eukaryotes and are known to associate with lipid droplets (LDs) and sites of LD-membrane contacts, with key roles in regulating lipid metabolism. They possess five domains, including an N-terminal transmembrane domain that anchors them to the endoplasmic reticulum, an RGS domain, a lipid interacting phox homology (PX) domain and two additional domains named the PXA and PXC domains of unknown structure and function. Here we report the crystal structure of the RGS domain of sorting nexin 25 (SNX25) and show that the AlphaFold2 prediction closely matches the experimental structure. Analysing the full-length SNX-RGS proteins across multiple homologues and species we find that the distant PXA and PXC domains in fact fold into a single unique structure that notably features a large and conserved hydrophobic pocket. The nature of this pocket strongly suggests a role in lipid or fatty acid binding, and we propose that these molecules represent a new class of conserved lipid transfer proteins. | |||
Structural Predictions of the SNX-RGS Proteins Suggest They Belong to a New Class of Lipid Transfer Proteins.,Paul B, Weeratunga S, Tillu VA, Hariri H, Henne WM, Collins BM Front Cell Dev Biol. 2022 Feb 3;10:826688. doi: 10.3389/fcell.2022.826688. , eCollection 2022. PMID:35223850<ref>PMID:35223850</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7sr2" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Sorting nexin 3D structures|Sorting nexin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Collins BM]] | [[Category: Collins BM]] | ||
[[Category: Paul B]] | [[Category: Paul B]] | ||
[[Category: Weeratunga S]] | [[Category: Weeratunga S]] | ||
Latest revision as of 19:54, 18 October 2023
Crystal structure of the human SNX25 regulator of G-protein signalling (RGS) domainCrystal structure of the human SNX25 regulator of G-protein signalling (RGS) domain
Structural highlights
FunctionSNX25_HUMAN May be involved in several stages of intracellular trafficking. Publication Abstract from PubMedRecent advances in protein structure prediction using machine learning such as AlphaFold2 and RosettaFold presage a revolution in structural biology. Genome-wide predictions of protein structures are providing unprecedented insights into their architecture and intradomain interactions, and applications have already progressed towards assessing protein complex formation. Here we present detailed analyses of the sorting nexin proteins that contain regulator of G-protein signalling domains (SNX-RGS proteins), providing a key example of the ability of AlphaFold2 to reveal novel structures with previously unsuspected biological functions. These large proteins are conserved in most eukaryotes and are known to associate with lipid droplets (LDs) and sites of LD-membrane contacts, with key roles in regulating lipid metabolism. They possess five domains, including an N-terminal transmembrane domain that anchors them to the endoplasmic reticulum, an RGS domain, a lipid interacting phox homology (PX) domain and two additional domains named the PXA and PXC domains of unknown structure and function. Here we report the crystal structure of the RGS domain of sorting nexin 25 (SNX25) and show that the AlphaFold2 prediction closely matches the experimental structure. Analysing the full-length SNX-RGS proteins across multiple homologues and species we find that the distant PXA and PXC domains in fact fold into a single unique structure that notably features a large and conserved hydrophobic pocket. The nature of this pocket strongly suggests a role in lipid or fatty acid binding, and we propose that these molecules represent a new class of conserved lipid transfer proteins. Structural Predictions of the SNX-RGS Proteins Suggest They Belong to a New Class of Lipid Transfer Proteins.,Paul B, Weeratunga S, Tillu VA, Hariri H, Henne WM, Collins BM Front Cell Dev Biol. 2022 Feb 3;10:826688. doi: 10.3389/fcell.2022.826688. , eCollection 2022. PMID:35223850[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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