8e0h

Crystal structure of human Sar1aD104/D140A double mutant

spinqualitylabelsall models 8e0h, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8e0h is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: G4P Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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). 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 Sar1a⋠ppGpp and Sar1b⋠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 Sar1a⋠ppGpp is more similar to Sar1b⋠GDP than to Sar1b⋠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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also GTP-binding protein 3D structures

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