6P5H

Structure of MavC middle insertion domain

Summary for 6P5H

• Entry DOI: 10.2210/pdb6p5h/pdb
• Descriptor: MavC (2 entities in total)
• Functional Keywords: ube2n, effector, mavc, protein binding
• Biological source: Legionella pneumophila
• Total number of polymer chains: 2
• Total formula weight: 24497.59

Authors

Negron Teron, K.I.,Puvar, K.,Iyer, S.,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

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: 32398758
DOI: 10.1038/s41467-020-16211-x

Experimental method

X-RAY DIFFRACTION (1.53 Å)