5V3N

Structure of S. cerevisiae Ulp2-Tof2-Csm1 complex

Summary for 5V3N

• Entry DOI: 10.2210/pdb5v3n/pdb
• Descriptor: Monopolin complex subunit CSM1, Ulp2p,Topoisomerase 1-associated factor 2 chimera (3 entities in total)
• Functional Keywords: monopolin, cohibin, rdna silencing, desumoylation, hydrolase
• Biological source: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast); More
• Total number of polymer chains: 2
• Total formula weight: 17261.18

Authors

SIngh, N.,Corbett, K.D. (deposition date: 2017-03-07, release date: 2017-05-17, Last modification date: 2023-10-04)

Primary citation

Liang, J.,Singh, N.,Carlson, C.R.,Albuquerque, C.P.,Corbett, K.D.,Zhou, H.
Recruitment of a SUMO isopeptidase to rDNA stabilizes silencing complexes by opposing SUMO targeted ubiquitin ligase activity.
Genes Dev., 31:802-815, 2017

PubMed Abstract: Post-translational modification by SUMO (small ubiquitin-like modifier) plays important but still poorly understood regulatory roles in eukaryotic cells, including as a signal for ubiquitination by SUMO targeted ubiquitin ligases (STUbLs). Here, we delineate the molecular mechanisms for SUMO-dependent control of ribosomal DNA (rDNA) silencing through the opposing actions of a STUbL (Slx5:Slx8) and a SUMO isopeptidase (Ulp2). We identify a conserved region in the Ulp2 C terminus that mediates its specificity for rDNA-associated proteins and show that this region binds directly to the rDNA-associated protein Csm1. Two crystal structures show that Csm1 interacts with Ulp2 and one of its substrates, the rDNA silencing protein Tof2, through adjacent conserved interfaces in its C-terminal domain. Disrupting Csm1's interaction with either Ulp2 or Tof2 dramatically reduces rDNA silencing and causes a marked drop in Tof2 abundance, suggesting that Ulp2 promotes rDNA silencing by opposing STUbL-mediated degradation of silencing proteins. Tof2 abundance is rescued by deletion of the STUbL or disruption of its SUMO-interacting motifs, confirming that Tof2 is targeted for degradation in a SUMO- and STUbL-dependent manner. Overall, our results demonstrate how the opposing actions of a localized SUMO isopeptidase and a STUbL regulate rDNA silencing by controlling the abundance of a key rDNA silencing protein, Tof2.

PubMed: 28487408
DOI: 10.1101/gad.296145.117

Experimental method

X-RAY DIFFRACTION (1.3 Å)