Deciphering the binding between Nupr1 and MSL1 and their DNA-repairing activity.
Deciphering the binding between Nupr1 and MSL1 and their DNA-repairing activity.
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DOI：
10.1371/journal.pone.0078101
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Iovanna JL
中科院分区：
文献类型：
--
作者：
Aguado-Llera D;Hamidi T;Doménech R;Pantoja-Uceda D;Gironella M;Santoro J;Velázquez-Campoy A;Neira JL;Iovanna JL
应激蛋白Nupr1是一种高度碱性、多功能、内在无序的蛋白质(IDP)。MSL1是一种组蛋白乙酰转移酶相关蛋白，已知可干预剂量补偿复合体(DCC)。在这项工作中，我们发现Nupr1和MSL1蛋白都被招募并形成复合体进入细胞核，以响应DNA损伤，这对于顺铂损伤的细胞生存是必不可少的。我们用光谱和生物物理方法研究了Nupr1和MSL1的相互作用，以及它们与DNA的结合亲和力。MSL1与Nupr1结合，在熵驱动的过程中具有中等亲和力(2.8µM)。MSL1不与未损伤的DNA结合，但它以中等亲和力(1.2微米)结合到化学损伤的DNA上，也是在熵驱动的过程中。Nupr1蛋白以略大的亲和力(0.4um)结合到化学损伤的DNA上，但是在热驱动的过程中。在与Nupr1或DNA形成的复合体中，Nupr1显示出不同的相互作用区域，但如核磁共振所示，它们总是无序的(模糊的)。这些结果强调了对Nupr1及其其他互动伙伴功能的随机描述。
The stress protein Nupr1 is a highly basic, multifunctional, intrinsically disordered protein (IDP). MSL1 is a histone acetyl transferase-associated protein, known to intervene in the dosage compensation complex (DCC). In this work, we show that both Nupr1 and MSL1 proteins were recruited and formed a complex into the nucleus in response to DNA-damage, which was essential for cell survival in reply to cisplatin damage. We studied the interaction of Nupr1 and MSL1, and their binding affinities to DNA by spectroscopic and biophysical methods. The MSL1 bound to Nupr1, with a moderate affinity (2.8 µM) in an entropically-driven process. MSL1 did not bind to non-damaged DNA, but it bound to chemically-damaged-DNA with a moderate affinity (1.2 µM) also in an entropically-driven process. The Nupr1 protein bound to chemically-damaged-DNA with a slightly larger affinity (0.4 µM), but in an enthalpically-driven process. Nupr1 showed different interacting regions in the formed complexes with Nupr1 or DNA; however, they were always disordered (“fuzzy”), as shown by NMR. These results underline a stochastic description of the functionality of the Nupr1 and its other interacting partners.
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