8e0h: Difference between revisions
New page: '''Unreleased structure''' The entry 8e0h is ON HOLD until Paper Publication Authors: Huang, Q. Description: Crystal structure of human Sar1aD104/D140A double mutant [[Category: Unrele... |
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==Crystal structure of human Sar1aD104/D140A double mutant== | |||
<StructureSection load='8e0h' size='340' side='right'caption='[[8e0h]], [[Resolution|resolution]] 2.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8e0h]] 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=8E0H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8E0H FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=G4P:GUANOSINE-5,3-TETRAPHOSPHATE'>G4P</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=8e0h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8e0h OCA], [https://pdbe.org/8e0h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8e0h RCSB], [https://www.ebi.ac.uk/pdbsum/8e0h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8e0h ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/SAR1A_HUMAN SAR1A_HUMAN] Involved in transport from the endoplasmic reticulum to the Golgi apparatus (By similarity). Required to maintain SEC16A localization at discrete locations on the ER membrane perhaps by preventing its dissociation. SAR1A-GTP-dependent assembly of SEC16A on the ER membrane forms an organized scaffold defining endoplasmic reticulum exit sites (ERES).<ref>PMID:17005010</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Transport of newly synthesized proteins from endoplasmic reticulum (ER) to Golgi is mediated by coat protein complex II (COPII). The assembly and disassembly of COPII vesicles is regulated by the molecular switch Sar1, which is a small GTPase and a component of COPII. Usually a small GTPase binds GDP (inactive form) or GTP (active form). Mammals have two Sar1 isoforms, Sar1a and Sar1b, that have approximately 90% sequence identity. Some experiments demonstrated that these two isoforms had distinct but overlapping functions. Here we found another instance of differing behavior: the alarmone ppGpp could bind to and inhibit the GTPase activity of human Sar1a but could not inhibit the GTPase activity of human Sar1b. The crystal structures of Sar1aâ
ppGpp and Sar1bâ
GDP have been determined. Superposition of the structures shows that ppGpp binds to the nucleotide-binding pocket, its guanosine base, ribose ring and 5'-diphosphate occupying nearly the same positions as for GDP. However, its 3'-diphosphate points away from the active site and, hence, away from the surface of the protein. The overall structure of Sar1aâ
ppGpp is more similar to Sar1bâ
GDP than to Sar1bâ
GTP. We also find that the Asp140-Arg138-water-ligand interaction net is important for the binding of ppGpp to Sar1a. This study provides further evidence showing that there are biochemical differences between the Sar1a and Sar1b isoforms of Sar1. | |||
The alarmone ppGpp selectively inhibits the isoform A of the human small GTPase Sar1.,Huang Q, Szebenyi DME Proteins. 2022 Nov 11. doi: 10.1002/prot.26445. PMID:36369712<ref>PMID:36369712</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Huang | <div class="pdbe-citations 8e0h" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Huang Q]] | |||
Latest revision as of 13:16, 25 October 2023
Crystal structure of human Sar1aD104/D140A double mutantCrystal structure of human Sar1aD104/D140A double mutant
Structural highlights
FunctionSAR1A_HUMAN Involved in transport from the endoplasmic reticulum to the Golgi apparatus (By similarity). Required to maintain SEC16A localization at discrete locations on the ER membrane perhaps by preventing its dissociation. SAR1A-GTP-dependent assembly of SEC16A on the ER membrane forms an organized scaffold defining endoplasmic reticulum exit sites (ERES).[1] Publication Abstract from PubMedTransport of newly synthesized proteins from endoplasmic reticulum (ER) to Golgi is mediated by coat protein complex II (COPII). The assembly and disassembly of COPII vesicles is regulated by the molecular switch Sar1, which is a small GTPase and a component of COPII. Usually a small GTPase binds GDP (inactive form) or GTP (active form). Mammals have two Sar1 isoforms, Sar1a and Sar1b, that have approximately 90% sequence identity. Some experiments demonstrated that these two isoforms had distinct but overlapping functions. Here we found another instance of differing behavior: the alarmone ppGpp could bind to and inhibit the GTPase activity of human Sar1a but could not inhibit the GTPase activity of human Sar1b. The crystal structures of Sar1aâ ppGpp and Sar1bâ GDP have been determined. Superposition of the structures shows that ppGpp binds to the nucleotide-binding pocket, its guanosine base, ribose ring and 5'-diphosphate occupying nearly the same positions as for GDP. However, its 3'-diphosphate points away from the active site and, hence, away from the surface of the protein. The overall structure of Sar1aâ ppGpp is more similar to Sar1bâ GDP than to Sar1bâ GTP. We also find that the Asp140-Arg138-water-ligand interaction net is important for the binding of ppGpp to Sar1a. This study provides further evidence showing that there are biochemical differences between the Sar1a and Sar1b isoforms of Sar1. The alarmone ppGpp selectively inhibits the isoform A of the human small GTPase Sar1.,Huang Q, Szebenyi DME Proteins. 2022 Nov 11. doi: 10.1002/prot.26445. PMID:36369712[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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