8ir2

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Rad18 interacts with the SMC5/6 localization factor 1 (SLF1) to recruit the SMC5/6 complex to DNA damage sites for repair. The mechanism of the specific Rad18 recognition by SLF1 is unclear. Here, we present the crystal structure of the tandem BRCT repeat (tBRCT) in SLF1 (SLF1(tBRCT)) bound with the interacting Rad18 peptide. Our structure and biochemical studies demonstrate that SLF1(tBRCT) interacts with two phosphoserines and adjacent residues in Rad18 for high-affinity and specificity Rad18 recognition. We found that SLF1(tBRCT) utilizes mechanisms common among tBRCTs as well as unique ones for Rad18 binding, the latter include interactions with an alpha-helical structure in Rad18 that has not been observed in other tBRCT-bound ligand proteins. Our work provides structural insights into Rad18 targeting by SLF1 and expands the understanding of BRCT-mediated complex assembly.
Rad18 interacts with the SMC5/6 localization factor 1 (SLF1) to recruit the SMC5/6 complex to DNA damage sites for repair. The mechanism of the specific Rad18 recognition by SLF1 is unclear. Here, we present the crystal structure of the tandem BRCT repeat (tBRCT) in SLF1 (SLF1(tBRCT)) bound with the interacting Rad18 peptide. Our structure and biochemical studies demonstrate that SLF1(tBRCT) interacts with two phosphoserines and adjacent residues in Rad18 for high-affinity and specificity Rad18 recognition. We found that SLF1(tBRCT) utilizes mechanisms common among tBRCTs as well as unique ones for Rad18 binding, the latter include interactions with an alpha-helical structure in Rad18 that has not been observed in other tBRCT-bound ligand proteins. Our work provides structural insights into Rad18 targeting by SLF1 and expands the understanding of BRCT-mediated complex assembly.
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Structural insights into Rad18 targeting by the SLF1 BRCT domains.,Huang W, Qiu F, Zheng L, Shi M, Shen M, Zhao X, Xiang S J Biol Chem. 2023 Sep 23;299(11):105288. doi: 10.1016/j.jbc.2023.105288. PMID:37748650<ref>PMID:37748650</ref>
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Structural insights into Rad18 targeting by the SLF1 BRCT domains.,Huang W, Qiu F, Zheng L, Shi M, Shen M, Zhao X, Xiang S J Biol Chem. 2023 Nov;299(11):105288. doi: 10.1016/j.jbc.2023.105288. Epub 2023 , Sep 23. PMID:37748650<ref>PMID:37748650</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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Crystal structure of the SLF1 BRCT domain in complex with a Rad18 peptide containing pS442 and pS444

PDB ID 8ir2

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