Recognition of SUMO-modified PCNA requires tandem receptor motifs in Srs2

摘要

细胞蛋白会发生各种各样的翻译后修饰。其中rn最常见的两种是短蛋白“泛素”或SLJMO的共rn价附着，这会促进蛋白-蛋白相互作用或引导rn蛋白的降解。PCNA(复制和修复中所涉及的rn一个因子)的“SLJMO化”(SLIMOylat{on)会吸rn收解旋酶Srs2。在这项研究中，Armstrorlg等rn人采用晶体学和生物化学方法解决了Srs2怎样rn识别被修饰的PCNA的问题。他们发现，两个rn“C-端主题”独立识别PCNA和ISLJMO，并且rn二者都是Srs2发挥功能所必需的。%Ubiquitin (Ub) and ubiquitin-like (Ub1) modifiers such as SUMO (also known as Smt3 in Saccharomyces cerevisiae) mediate signal transduction through post-translational modification of substrate proteins in pathways that control differentiation, apoptosis and the cell cycle, and responses to stress such as the DNA damage response. In yeast, the proliferating cell nuclear antigen PCNA (also known as Pol30) is modified by ubiquitin in response to DNA damage and by SUMO during S phase. Whereas Ub-PCNA can signal for recruitment of translesion DNA polymerases, SUMO-PCNA signals for recruitment of the anti-recombinogenic DNA helicase Srs2. It remains unclear how receptors such as Srs2 specifically recognize substrates after conjugation to Ub and Ubls. Here we show, through structural, biochemical and functional studies, that the Srs2 carboxy-terminal domain harbours tandem receptor motifs that interact independently with PCNA and SUMO and that both motifs are required to recognize SUMO-PCNA specifically. The mechanism presented is pertinent to understanding how other receptors specifically recognize Ub- and Ubl-modified substrates to facilitate signal transduction.