Structural basis for the E3 ligase activity enhancement of yeast Nse2 by SUMO-interacting motifs

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 maintenanc...

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Detalles Bibliográficos
Autores: Varejão, Nathalia|||0000-0002-6952-8896, Lascorz Lozano, Jara A.|||0000-0002-5823-0728, Codina-Fabra, Joan|||0000-0002-6147-618X, Bellí, Gemma|||0000-0002-4161-3204, Borràs-Gas, Helena|||0000-0002-3633-9132, Torres-Rosell, Jordi|||0000-0003-1308-6926, Reverter Cendrós, David|||0000-0002-5347-0992
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:303203
Acceso en línea:https://ddd.uab.cat/record/303203
https://dx.doi.org/urn:doi:10.1038/s41467-021-27301-9
Access Level:acceso abierto
Palabra clave:X-ray crystallography
Enzyme mechanisms
Ubiquitin ligases
Descripción
Sumario: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.