An NTP-binding motif is the most conserved sequence in a highly diverged monophyletic group of proteins involved in positive strand RNA viral replication.

An NTP-binding motif is the most conserved sequence in a highly diverged monophyletic group of proteins involved in positive strand RNA viral replication.
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DOI:
10.1007/bf02102483
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发表时间:
1989-03
影响因子:
3.9
通讯作者:
Koonin EV
Koonin EV
中科院分区:
生物学3区
文献类型:
--
作者:
Gorbalenya AE;Blinov VM;Donchenko AP;Koonin EV

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在几组正链RNA病毒的非结构蛋白中发现了NTP基序,这是许多利用NTP的酶的共同特征。这些组包括感染动物的微核型、甲型和冠状病毒,以及植物的复合病毒、斑点病毒、烟草病毒、三角病毒、霍代病毒和新城疫病毒,共计21种病毒。已有研究表明,含NTP基序的病毒蛋白由三个不同的家族组成,每个家族内的序列在统计学上具有极高的相似性。这两个家族之间的相似性也较低,但仍然有效。已经产生了一个整体比对,其中包括几个高度保守的序列延伸。后者中最突出的两个包含NTP基序的所谓“A”和“B”位点,在这些序列中观察到五个不变氨基酸残基中的四个。这些观察结果与病毒多结构域蛋白中各蛋白(结构域)位置的比较分析结果相结合,表明正链RNA病毒的所有含NTP基序的蛋白都是同源的,构成了一个高度分化的单系类群。在这一组中,NTP基序的“A”和“B”位点是最保守的序列,根据推断,它们应该在蛋白质的功能中发挥主要作用。假设所有这些蛋白都具有NTP结合能力和可能的NTPase活性,在病毒RNA复制中发挥一些NTP依赖的功能。强调了系统发育分析对于评估蛋白质中NTP基序(以及这类序列基序)的重要性的重要性。
NTP-motif, a consensus sequence previously shown to be characteristic of numerous NTP-utilizing enzymes, was identified in nonstructural proteins of several groups of positive-strand RNA viruses. These groups include picorna-, alpha-, and coronaviruses infecting animals and como-, poty-, tobamo-, tricorna-, hordei-, and furoviruses of plants, totalling 21 viruses. It has been demonstrated that the viral NTP-motif-containing proteins constitute three distinct families, the sequences within each family being similar to each other at a statistically highly significant level. A lower, but still valid similarity has also been revealed between the families. An overall alignment has been generated, which includes several highly conserved sequence stretches. The two most prominent of the latter contain the socalled “A” and “B” sites of the NTP-motif, with four of the five invariant amino acid residues observed within these sequences. These observations, taken together with the results of comparative analysis of the positions occupied by respective proteins (domains) in viral multidomain proteins, suggest that all the NTP-motif-containing proteins of positive-strand RNA viruses are homologous, constituting a highly diverged monophyletic group. In this group the “A” and “B” sites of the NTP-motif are the most conserved sequences and, by inference, should play the principal role in the functioning of the proteins. A hypothesis is proposed that all these proteins posses NTP-binding capacity and possibly NTPase activity, performing some NTP-dependent function in viral RNA replication. The importance of phylogenetic analysis for the assessment of the significance of the occurrence of the NTP-motif (and of sequence motifs of this sort in general) in proteins is emphasized.