6P5B
Crystal Structure of MavC in Complex with Ub-UbE2N
Summary for 6P5B
| Entry DOI | 10.2210/pdb6p5b/pdb |
| Descriptor | MavC, Ubiquitin-conjugating enzyme E2 N, Ubiquitin, ... (4 entities in total) |
| Functional Keywords | ubiquitin, effector, ligase, transglutaminase, transferase |
| Biological source | Legionella pneumophila More |
| Total number of polymer chains | 3 |
| Total formula weight | 69929.55 |
| Authors | Puvar, K.,Iyer, S.,Negron Teron, K.I.,Das, C. (deposition date: 2019-05-30, release date: 2020-05-27, Last modification date: 2023-10-11) |
| Primary citation | Puvar, K.,Iyer, S.,Fu, J.,Kenny, S.,Negron Teron, K.I.,Luo, Z.Q.,Brzovic, P.S.,Klevit, R.E.,Das, C. Legionella effector MavC targets the Ube2N~Ub conjugate for noncanonical ubiquitination. Nat Commun, 11:2365-2365, 2020 Cited by PubMed Abstract: The bacterial effector MavC modulates the host immune response by blocking Ube2N activity employing an E1-independent ubiquitin ligation, catalyzing formation of a γ-glutamyl-ε-Lys (Gln40-Lys92) 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. PubMed: 32398758DOI: 10.1038/s41467-020-16211-x PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.099 Å) |
Structure validation
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