Sauguet Ludovic, Raia Pierre, Henneke Ghislaine, Delarue Marc
Unit of Structural Dynamics of Macromolecules, Pasteur Institute and CNRS UMR 3528, 75015 Paris, France.
Pierre and Marie Curie University, Paris 6, 75006 Paris, France.
Nat Commun. 2016;7:12227. doi: 10.1038/ncomms12227. Epub 2016 Aug 22.
Archaeal replicative DNA polymerase D (PolD) constitute an atypical class of DNA polymerases made of a proofreading exonuclease subunit (DP1) and a larger polymerase catalytic subunit (DP2), both with unknown structures. We have determined the crystal structures of Pyrococcus abyssi DP1 and DP2 at 2.5 and 2.2 Å resolution, respectively, revealing a catalytic core strikingly different from all other known DNA polymerases (DNAPs). Rather, the PolD DP2 catalytic core has the same 'double-psi β-barrel' architecture seen in the RNA polymerase (RNAP) superfamily, which includes multi-subunit transcriptases of all domains of life, homodimeric RNA-silencing pathway RNAPs and atypical viral RNAPs. This finding bridges together, in non-viral world, DNA transcription and DNA replication within the same protein superfamily. This study documents further the complex evolutionary history of the DNA replication apparatus in different domains of life and proposes a classification of all extant DNAPs.
古菌复制性DNA聚合酶D（PolD）是一类非典型的DNA聚合酶，由一个校对核酸外切酶亚基（DP1）和一个较大的聚合酶催化亚基（DP2）组成，二者结构均未知。我们分别以2.5埃和2.2埃的分辨率测定了深渊嗜热栖热菌DP1和DP2的晶体结构，揭示出一个与所有其他已知DNA聚合酶（DNAP）显著不同的催化核心。相反，PolD DP2催化核心具有在RNA聚合酶（RNAP）超家族中所见的相同“双ψβ桶”结构，该超家族包括生命所有域的多亚基转录酶、同二聚体RNA沉默途径RNAP和非典型病毒RNAP。这一发现将非病毒世界中的DNA转录和DNA复制在同一蛋白质超家族中联系起来。这项研究进一步记录了不同生命域中DNA复制装置复杂的进化历史，并提出了所有现存DNAP的分类。
