7T5P

Cryo-EM structure of human SIMC1-SLF2 complex

Summary for 7T5P

• Entry DOI: 10.2210/pdb7t5p/pdb
• EMDB information: 25706
• Descriptor: SUMO-interacting motif-containing protein 1, SMC5-SMC6 complex localization factor protein 2 (2 entities in total)
• Functional Keywords: nse5, nse6, smc5, smc6, simc1, slf2, c5orf25, viral restriction, antiviral protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 128889.33

Authors

Maeda, S.,Oravcova, M.,Boddy, M.N.,Otomo, T. (deposition date: 2021-12-13, release date: 2022-12-07, Last modification date: 2024-06-05)

Primary citation

Oravcova, M.,Nie, M.,Zilio, N.,Maeda, S.,Jami-Alahmadi, Y.,Lazzerini-Denchi, E.,Wohlschlegel, J.A.,Ulrich, H.D.,Otomo, T.,Boddy, M.
The Nse5/6-like SIMC1-SLF2 complex localizes SMC5/6 to viral replication centers.
Elife, 11:-, 2022

PubMed Abstract: The human SMC5/6 complex is a conserved guardian of genome stability and an emerging component of antiviral responses. These disparate functions likely require distinct mechanisms of SMC5/6 regulation. In yeast, Smc5/6 is regulated by its Nse5/6 subunits, but such regulatory subunits for human SMC5/6 are poorly defined. Here, we identify a novel SMC5/6 subunit called SIMC1 that contains SUMO interacting motifs (SIMs) and an Nse5-like domain. We isolated SIMC1 from the proteomic environment of SMC5/6 within polyomavirus large T antigen (LT)-induced subnuclear compartments. SIMC1 uses its SIMs and Nse5-like domain to localize SMC5/6 to polyomavirus replication centers (PyVRCs) at SUMO-rich PML nuclear bodies. SIMC1's Nse5-like domain binds to the putative Nse6 orthologue SLF2 to form an anti-parallel helical dimer resembling the yeast Nse5/6 structure. SIMC1-SLF2 structure-based mutagenesis defines a conserved surface region containing the N-terminus of SIMC1's helical domain that regulates SMC5/6 localization to PyVRCs. Furthermore, SLF1, which recruits SMC5/6 to DNA lesions via its BRCT and ARD motifs, binds SLF2 analogously to SIMC1 and forms a separate Nse5/6-like complex. Thus, two Nse5/6-like complexes with distinct recruitment domains control human SMC5/6 localization.

PubMed: 36373674
DOI: 10.7554/eLife.79676

Experimental method

ELECTRON MICROSCOPY (3.4 Å)