Ribonuclease A homologues of the zebrafish: polymorphism, crystal structures of two representatives and their evolutionary implications.

Ribonuclease A homologues of the zebrafish: polymorphism, crystal structures of two representatives and their evolutionary implications.
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DOI:
10.1016/j.jmb.2008.04.070
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发表时间:
2008-06-27
影响因子:
5.6
通讯作者:
Acharya, K. Ravi
Acharya, K. Ravi
中科院分区:
生物学2区
文献类型:
--
作者:
Kazakou, Konstantina;Holloway, Daniel E.;Prior, Stephen H.;Subramanian, Vasanta;Acharya, K. Ravi

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核糖核酸酶A(RNase A)超家族的广泛和功能多样的成员提供了一个很好的机会来研究保守蛋白质支架上工作的进化力量。来自斑马鱼的代表特别令人感兴趣,因为与非鱼类同源物的进化距离很大。我们进行了详尽的调查,现有的斑马鱼DNA序列,并发现显着的多态性之间的四个已知的同源物。在先前命名法的扩展中,变体被命名为RNA酶ZF-1a-c、ZF-2a-d、ZF-3a-e和ZF-4。我们提出了第一个X射线晶体结构的斑马鱼核糖核酸酶,RNA酶ZF-1a和-3e在1.35和1.85毫米分辨率,分别。基于结构的聚类与其他10种核糖核酸酶结构表明与哺乳动物血管生成素和两栖动物核糖核酸酶的相似性最大,并支持所有现今核糖核酸酶都是从具有三个二硫键的祖先进化而来的观点。在它们的细节中,这两种结构是其他脊椎动物核糖核酸酶中存在的特征的有趣的熔炉。而在RNase ZF-1a中,活性位点被C-末端区段阻塞(如在血管生成素中观察到的),在RNase ZF-3e中,相同的区域是开放的(如在更催化有效的同源物中观察到的)。现今核糖核酸酶的祖先更可能具有阻塞性C末端,并且RNA酶ZF-1和ZF-3的相对高的相似性(晚期分歧)推断活性位点解除阻塞事件独立地发生在不同的脊椎动物谱系中。
The widespread and functionally varied members of the ribonuclease A (RNase A) superfamily provide an excellent opportunity to study evolutionary forces at work on a conserved protein scaffold. Representatives from the zebrafish are of particular interest as the evolutionary distance from non-ichthyic homologues is large. We conducted an exhaustive survey of available zebrafish DNA sequences and found significant polymorphism among its four known homologues. In an extension of previous nomenclature, the variants have been named RNases ZF-1a–c,-2a–d,-3a–e and-4. We present the first X-ray crystal structures of zebrafish ribonucleases, RNases ZF-1a and-3e at 1.35-and 1.85 Å resolution, respectively. Structure-based clustering with ten other ribonuclease structures indicates greatest similarity to mammalian angiogenins and amphibian ribonucleases, and supports the view that all present-day ribonucleases evolved from a progenitor with three disulphide bonds. In their details, the two structures are intriguing melting-pots of features present in ribonucleases from other vertebrate classes. Whereas in RNase ZF-1a the active site is obstructed by the C-terminal segment (as observed in angiogenin), in RNase ZF-3e the same region is open (as observed in more catalytically efficient homologues). The progenitor of present-day ribonucleases is more likely to have had an obstructive C terminus, and the relatively high similarity (late divergence) of RNases ZF-1 and-3 infers that the active site unblocking event has happened independently in different vertebrate lineages.
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