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A new insight into protein-protein interactions and the effect of conformational alterations in PCNA.
International Journal of Biological Macromolecules ( IF 8.2 ) Pub Date : 2020-01-22 , DOI: 10.1016/j.ijbiomac.2020.01.212
Vijay Kumar Bhardwaj 1 , Rituraj Purohit 1
Affiliation  

The sliding clamp proteins are present in almost all forms of life and participate in various fundamental processes. Many of these proteins accommodate a conserved sequence that interacts with the hydrophobic groove on sliding clamps. The conserved sequence on proteins is known as the PCNA-interacting protein box, and the hydrophobic groove of PCNA contains regions of the inter-domain connecting loop, the central loop, and amino acids from the C-terminal tail of PCNA. We performed molecular dynamics simulation studies (1.0 μs) to analyze the structural changes at the atomic level in native, C22Y, and C81R mutant PCNA. Our study revealed significant changes at sites responsible for a functional trimeric form of PCNA. This study also unveils the dynamic behavior of IDCL, central loop, and the C-terminal tail, which are essential regions for protein binding with PCNA and also sheds light on the effect of mutations on binding with the Cdc9 peptide. The observation of Cdc9 peptide complexed with native and mutants (C22Y and C81R) structures possibly reveals the mechanism by which PCNA recruits different proteins required for various biological processes and also highlights the importance of dynamic behavior of key regions involved in PCNA protein-protein interactions.

中文翻译:

对蛋白质相互作用和PCNA构象改变的影响的新见解。

滑动夹蛋白几乎存在于所有生命形式中,并参与各种基本过程。这些蛋白质中的许多蛋白质都具有与滑动夹具上的疏水性凹槽相互作用的保守序列。蛋白质上的保守序列称为与PCNA相互作用的蛋白盒,PCNA的疏水沟包含域间连接环,中央环和PCNA C末端尾部的氨基酸。我们进行了分子动力学模拟研究(1.0μs),以分析天然,C22Y和C81R突变型PCNA在原子水平上的结构变化。我们的研究表明,负责PCNA功能三聚体形式的位点发生了显着变化。这项研究还揭示了IDCL,中心环和C端尾部的动态行为,这是蛋白质与PCNA结合的关键区域,也阐明了突变对与Cdc9肽结合的影响。与天然和突变体(C22Y和C81R)结构复合的Cdc9肽的观察可能揭示了PCNA募集各种生物学过程所需的不同蛋白质的机制,也强调了参与PCNA蛋白质-蛋白质相互作用的关键区域动态行为的重要性。
更新日期:2020-01-22
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