Structural Basis for the E3 Ligase Activity Enhancement of Yeast Nse2 by SUMO-interacting Motifs

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Dec 2

PMID 34853311

Citations 14

Authors

Nathalia Varejao

Jara Lascorz

Joan Codina-Fabra

Gemma Belli

Helena Borras-Gas

Jordi Torres-Rosell

David Reverter

Affiliations

Soon will be listed here.

Abstract

Post-translational modification of proteins by ubiquitin and ubiquitin-like modifiers, such as SUMO, are key events in protein homeostasis or DNA damage response. Smc5/6 is a nuclear multi-subunit complex that participates in the recombinational DNA repair processes and is required in the maintenance of chromosome integrity. Nse2 is a subunit of the Smc5/6 complex that possesses SUMO E3 ligase activity by the presence of a SP-RING domain that activates the E2~SUMO thioester for discharge on the substrate. Here we present the crystal structure of the SUMO E3 ligase Nse2 in complex with an E2-SUMO thioester mimetic. In addition to the interface between the SP-RING domain and the E2, the complex reveals how two SIM (SUMO-Interacting Motif) -like motifs in Nse2 are restructured upon binding the donor and E2-backside SUMO during the E3-dependent discharge reaction. Both SIM interfaces are essential in the activity of Nse2 and are required to cope with DNA damage.

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