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| | <StructureSection load='4xwo' size='340' side='right'caption='[[4xwo]], [[Resolution|resolution]] 2.75Å' scene=''> | | <StructureSection load='4xwo' size='340' side='right'caption='[[4xwo]], [[Resolution|resolution]] 2.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4xwo]] is a 28 chain structure with sequence from [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XWO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XWO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4xwo]] is a 28 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae], [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XWO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XWO FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</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=4xwo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xwo OCA], [https://pdbe.org/4xwo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xwo RCSB], [https://www.ebi.ac.uk/pdbsum/4xwo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xwo ProSAT]</span></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4xtr|4xtr]], [[4xvu|4xvu]]</td></tr>
| + | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GET3, ARR4, YDL100C, D2371 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast])</td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4xwo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xwo OCA], [http://pdbe.org/4xwo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xwo RCSB], [http://www.ebi.ac.uk/pdbsum/4xwo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xwo ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GET3_YEAST GET3_YEAST]] ATPase required for the post-translational delivery of tail-anchored (TA) proteins to the endoplasmic reticulum. Recognizes and selectively binds the transmembrane domain of TA proteins in the cytosol. This complex then targets to the endoplasmic reticulum by membrane-bound receptors GET1 and GET2, where the tail-anchored protein is released for insertion. This process is regulated by ATP binding and hydrolysis. ATP binding drives the homodimer towards the closed dimer state, facilitating recognition of newly synthesized TA membrane proteins. ATP hydrolysis is required for insertion. Subsequently, the homodimer reverts towards the open dimer state, lowering its affinity for the GET1-GET2 receptor, and returning it to the cytosol to initiate a new round of targeting. Cooperates with the HDEL receptor ERD2 to mediate the ATP-dependent retrieval of resident ER proteins that contain a C-terminal H-D-E-L retention signal from the Golgi to the ER. Involved in low-level resistance to the oxyanions arsenite and arsenate, and in heat tolerance.<ref>PMID:12680698</ref> <ref>PMID:16269340</ref> <ref>PMID:18724936</ref> <ref>PMID:21866104</ref> <ref>PMID:21719644</ref> | + | [https://www.uniprot.org/uniprot/GET3_YEAST GET3_YEAST] ATPase required for the post-translational delivery of tail-anchored (TA) proteins to the endoplasmic reticulum. Recognizes and selectively binds the transmembrane domain of TA proteins in the cytosol. This complex then targets to the endoplasmic reticulum by membrane-bound receptors GET1 and GET2, where the tail-anchored protein is released for insertion. This process is regulated by ATP binding and hydrolysis. ATP binding drives the homodimer towards the closed dimer state, facilitating recognition of newly synthesized TA membrane proteins. ATP hydrolysis is required for insertion. Subsequently, the homodimer reverts towards the open dimer state, lowering its affinity for the GET1-GET2 receptor, and returning it to the cytosol to initiate a new round of targeting. Cooperates with the HDEL receptor ERD2 to mediate the ATP-dependent retrieval of resident ER proteins that contain a C-terminal H-D-E-L retention signal from the Golgi to the ER. Involved in low-level resistance to the oxyanions arsenite and arsenate, and in heat tolerance.<ref>PMID:12680698</ref> <ref>PMID:16269340</ref> <ref>PMID:18724936</ref> <ref>PMID:21866104</ref> <ref>PMID:21719644</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | *[[ATPase 3D structures|ATPase 3D structures]] | | *[[ATPase 3D structures|ATPase 3D structures]] |
| | *[[Antibody 3D structures|Antibody 3D structures]] | | *[[Antibody 3D structures|Antibody 3D structures]] |
| | + | *[[3D structures of human antibody|3D structures of human antibody]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Baker's yeast]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Chang, H Y]] | + | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: Hegde, R S]] | + | [[Category: Saccharomyces cerevisiae S288C]] |
| - | [[Category: Keenan, R J]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Kossiakoff, A A]] | + | [[Category: Chang H-Y]] |
| - | [[Category: Mateja, A]] | + | [[Category: Hegde RS]] |
| - | [[Category: Paduch, M]] | + | [[Category: Keenan RJ]] |
| - | [[Category: Szydlowska, A]] | + | [[Category: Kossiakoff AA]] |
| - | [[Category: Hydrolase-transport protein complex]] | + | [[Category: Mateja A]] |
| - | [[Category: Membrane protein targeting complex]] | + | [[Category: Paduch M]] |
| | + | [[Category: Szydlowska A]] |
| Structural highlights
4xwo is a 28 chain structure with sequence from Homo sapiens, Saccharomyces cerevisiae, Saccharomyces cerevisiae S288C and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
GET3_YEAST ATPase required for the post-translational delivery of tail-anchored (TA) proteins to the endoplasmic reticulum. Recognizes and selectively binds the transmembrane domain of TA proteins in the cytosol. This complex then targets to the endoplasmic reticulum by membrane-bound receptors GET1 and GET2, where the tail-anchored protein is released for insertion. This process is regulated by ATP binding and hydrolysis. ATP binding drives the homodimer towards the closed dimer state, facilitating recognition of newly synthesized TA membrane proteins. ATP hydrolysis is required for insertion. Subsequently, the homodimer reverts towards the open dimer state, lowering its affinity for the GET1-GET2 receptor, and returning it to the cytosol to initiate a new round of targeting. Cooperates with the HDEL receptor ERD2 to mediate the ATP-dependent retrieval of resident ER proteins that contain a C-terminal H-D-E-L retention signal from the Golgi to the ER. Involved in low-level resistance to the oxyanions arsenite and arsenate, and in heat tolerance.[1] [2] [3] [4] [5]
Publication Abstract from PubMed
Tail-anchored (TA) proteins are a physiologically important class of membrane proteins targeted to the endoplasmic reticulum by the conserved guided-entry of TA proteins (GET) pathway. During transit, their hydrophobic transmembrane domains (TMDs) are chaperoned by the cytosolic targeting factor Get3, but the molecular nature of the functional Get3-TA protein targeting complex remains unknown. We reconstituted the physiologic assembly pathway for a functional targeting complex and showed that it comprises a TA protein bound to a Get3 homodimer. Crystal structures of Get3 bound to different TA proteins showed an alpha-helical TMD occupying a hydrophobic groove that spans the Get3 homodimer. Our data elucidate the mechanism of TA protein recognition and shielding by Get3 and suggest general principles of hydrophobic domain chaperoning by cellular targeting factors.
Protein targeting. Structure of the Get3 targeting factor in complex with its membrane protein cargo.,Mateja A, Paduch M, Chang HY, Szydlowska A, Kossiakoff AA, Hegde RS, Keenan RJ Science. 2015 Mar 6;347(6226):1152-5. doi: 10.1126/science.1261671. PMID:25745174[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Shen J, Hsu CM, Kang BK, Rosen BP, Bhattacharjee H. The Saccharomyces cerevisiae Arr4p is involved in metal and heat tolerance. Biometals. 2003 Sep;16(3):369-78. PMID:12680698
- ↑ Schuldiner M, Collins SR, Thompson NJ, Denic V, Bhamidipati A, Punna T, Ihmels J, Andrews B, Boone C, Greenblatt JF, Weissman JS, Krogan NJ. Exploration of the function and organization of the yeast early secretory pathway through an epistatic miniarray profile. Cell. 2005 Nov 4;123(3):507-19. PMID:16269340 doi:S0092-8674(05)00868-8
- ↑ Schuldiner M, Metz J, Schmid V, Denic V, Rakwalska M, Schmitt HD, Schwappach B, Weissman JS. The GET complex mediates insertion of tail-anchored proteins into the ER membrane. Cell. 2008 Aug 22;134(4):634-45. PMID:18724936 doi:S0092-8674(08)00777-0
- ↑ Mariappan M, Mateja A, Dobosz M, Bove E, Hegde RS, Keenan RJ. The mechanism of membrane-associated steps in tail-anchored protein insertion. Nature. 2011 Aug 24;477(7362):61-6. doi: 10.1038/nature10362. PMID:21866104 doi:10.1038/nature10362
- ↑ Stefer S, Reitz S, Wang F, Wild K, Pang YY, Schwarz D, Bomke J, Hein C, Lohr F, Bernhard F, Denic V, Dotsch V, Sinning I. Structural Basis for Tail-Anchored Membrane Protein Biogenesis by the Get3-Receptor Complex. Science. 2011 Jun 30. PMID:21719644 doi:10.1126/science.1207125
- ↑ Mateja A, Paduch M, Chang HY, Szydlowska A, Kossiakoff AA, Hegde RS, Keenan RJ. Protein targeting. Structure of the Get3 targeting factor in complex with its membrane protein cargo. Science. 2015 Mar 6;347(6226):1152-5. doi: 10.1126/science.1261671. PMID:25745174 doi:http://dx.doi.org/10.1126/science.1261671
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