TY - JOUR
T1 - Structural basis for the E3 ligase activity enhancement of yeast Nse2 by SUMO-interacting motifs
AU - Varejão, Nathalia
AU - Lascorz, Jara
AU - Codina-Fabra, Joan
AU - Bellí, Gemma
AU - Borràs-Gas, Helena
AU - Torres-Rosell, Jordi
AU - Reverter, David
N1 - Funding Information:
DR acknowledges support from the Serra Hunter program from Generalitat de Cata-lunya. X-ray experiments were performed at BL-13 Xaloc beamline at ALBA Synchrotron with the collaboration of ALBA staff.
Funding Information:
This work was supported by grants from the “Ministerio de Ciencia, Innovación y Universidades” PGC2018-098423-B-I00 to DR and PGC2018-097796-B-I00 to JT-R and by grant 2017-SGR-569 from “AGAUR-Generalitat de Catalunya” to JT-R.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85120179687&partnerID=8YFLogxK
U2 - 10.1038/s41467-021-27301-9
DO - 10.1038/s41467-021-27301-9
M3 - Article
C2 - 34853311
VL - 12
IS - 1
M1 - 7013
ER -