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-Structure paper
タイトル | The Nse5/6-like SIMC1-SLF2 complex localizes SMC5/6 to viral replication centers. |
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ジャーナル・号・ページ | Elife, Vol. 11, Year 2022 |
掲載日 | 2022年11月14日 |
著者 | Martina Oravcová / Minghua Nie / Nicola Zilio / Shintaro Maeda / Yasaman Jami-Alahmadi / Eros Lazzerini-Denchi / James A Wohlschlegel / Helle D Ulrich / Takanori Otomo / Michael N Boddy / |
PubMed 要旨 | 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 ...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. |
リンク | Elife / PubMed:36373674 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.4 Å |
構造データ | EMDB-25706, PDB-7t5p: |
由来 |
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キーワード | ANTIVIRAL PROTEIN / Nse5 / Nse6 / SMC5 / SMC6 / SIMC1 / SLF2 / C5orf25 / viral restriction |