6i7h

Crystal structure of dimeric FICD mutant K256S

spinqualitylabelsall models 6i7h, resolution 2.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6i7h is a 1 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 2.25Å Ligands: MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function FICD_HUMAN Adenylyltransferase that mediates the addition of adenosine 5'-monophosphate (AMP) to specific residues of target proteins. Able to inactivate Rho GTPases in vitro by adding AMP to RhoA, Rac and Cdc42. It is however unclear whether it inactivates GTPases in vivo and physiological substrates probably remain to be identified. Publication Abstract from PubMed AMPylation is an inactivating modification that alters the activity of the major endoplasmic reticulum (ER) chaperone BiP to match the burden of unfolded proteins. A single ER-localised Fic protein, FICD (HYPE), catalyses both AMPylation and deAMPylation of BiP. However, the basis for the switch in FICD's activity is unknown. We report on the transition of FICD from a dimeric enzyme, that deAMPylates BiP, to a monomer with potent AMPylation activity. Mutations in the dimer interface, or of residues along an inhibitory pathway linking the dimer interface to the enzyme's active site, favour BiP AMPylation in vitro and in cells. Mechanistically, monomerisation relieves a repressive effect allosterically propagated from the dimer interface to the inhibitory Glu234, thereby permitting AMPylation-competent binding of MgATP. Moreover, a reciprocal signal, propagated from the nucleotide-binding site, provides a mechanism for coupling the oligomeric state and enzymatic activity of FICD to the energy status of the ER. An oligomeric state-dependent switch in the ER enzyme FICD regulates AMPylation and deAMPylation of BiP.,Perera LA, Rato C, Yan Y, Neidhardt L, McLaughlin SH, Read RJ, Preissler S, Ron D EMBO J. 2019 Sep 18:e102177. doi: 10.15252/embj.2019102177. PMID:31531998 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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