6ulh
Structure of MavC in complex with its substrate in R3 spacegroupStructure of MavC in complex with its substrate in R3 spacegroup
Structural highlights
Publication Abstract from PubMedThe 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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