6ums

Crystal structure of MavC in complex with its substrate mimic in C222(1) space group

spinqualitylabelsall models 6ums, resolution 2.34Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.344Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The bacterial effector MavC modulates the host immune response by blocking Ube2N activity employing an E1-independent ubiquitin ligation, catalyzing formation of a gamma-glutamyl-epsilon-Lys (Gln40(Ub)-Lys92(Ube2N)) isopeptide crosslink using a transglutaminase mechanism. Here we provide biochemical evidence in support of MavC targeting the activated, thioester-linked Ube2N~ubiquitin conjugate, catalyzing an intramolecular transglutamination reaction, covalently crosslinking the Ube2N and Ub subunits effectively inactivating the E2~Ub conjugate. Ubiquitin exhibits weak binding to MavC alone, but shows an increase in affinity when tethered to Ube2N in a disulfide-linked substrate that mimics the charged E2~Ub conjugate. Crystal structures of MavC in complex with the substrate mimic and crosslinked product provide insights into the reaction mechanism and underlying protein dynamics that favor transamidation over deamidation, while revealing a crucial role for the structurally unique insertion domain in substrate recognition. This work provides a structural basis of ubiquitination by transglutamination and identifies this enzyme's true physiological substrate. Legionella effector MavC targets the Ube2N~Ub conjugate for noncanonical ubiquitination.,Puvar K, Iyer S, Fu J, Kenny S, Negron Teron KI, Luo ZQ, Brzovic PS, Klevit RE, Das C Nat Commun. 2020 May 12;11(1):2365. doi: 10.1038/s41467-020-16211-x. PMID:32398758 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also 3D structures of ubiquitin 3D structures of ubiquitin conjugating enzyme

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