A novel family of P-loop NTPases with an unusual phyletic distribution and transmembrane segments inserted within the NTPase domain.

A novel family of P-loop NTPases with an unusual phyletic distribution and transmembrane segments inserted within the NTPase domain.
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DOI:
10.1186/gb-2004-5-5-r30
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发表时间:
2004
期刊:
影响因子:
12.3
通讯作者:
Koonin EV
Koonin EV
中科院分区:
生物学1区
文献类型:
--
作者:
Aravind L;Iyer LM;Leipe DD;Koonin EV

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这项研究的特点KAP蛋白家族-一个新发现的亚组的P-环NTPases,其中有跨膜螺旋插入到P-环NTPases结构域。它们不寻常的系统分布表明KAP蛋白通过水平基因转移从细菌转移到动物。最近的序列结构研究的P-环折叠NTPases有很大的进步,现有的理解,其进化和功能多样性。这些研究提供了一个框架内的新的谱系特征,这一折叠和预测其功能特性。使用序列分析搜索和同源性为基础的结构预测,我们已经确定了一个以前未表征的家庭的P-环NTPases,其中包括神经元膜蛋白和受体酪氨酸激酶底物Kidins 220/ARMS,这是保守的动物,F-质粒PifA蛋白参与噬菌体T7排斥,和几个未表征的细菌蛋白。我们将这些(预测的)NTPases称为KAP家族,位于Kidins 220/ARMS和PifA之后。KAP家族NTPases在细菌中广泛分布,但在真核生物中仅在动物中存在。许多原核KAP NTPases在质粒中编码,并且倾向于经历破坏以形成假基因。所有真核生物和某些细菌KAP NTPases的独特特征是存在两个或四个跨膜螺旋插入P环NTPases结构域。这些跨膜螺旋将锚KAP NTPases锚定在膜中,使得P环结构域位于细胞内侧。我们表明,KAP家族属于相同的主要部门的P-环NTR折叠与AAA+,ABC,RecA样,VirD 4样,PilT样,AP/NACHT样NTR类。除了KAP家族外,我们还鉴定了另一个预测的细菌NTPases小家族,其具有插入到P环结构域中的两个跨膜螺旋。该家族与KAP NTPases没有特异性相关,表明跨膜螺旋的独立获得。我们预测,KAP家族NTPases的功能主要是在蛋白质复合物的NTP依赖的动力学,特别是那些与细胞膜的细胞内表面。动物KAP NTPases,包括Kidins 220/ARMS,可能作为参与神经突生长和发育的膜相关信号复合物组装的NTP依赖性调节剂发挥作用。原核KAP NTPases的一个可能的功能可能是从宿主细胞中排除自私的复制子,如病毒。系统发育分析和系统模式表明,动物的共同祖先获得了一个KAP NTR通过横向转移从细菌。然而,不能排除早期转移到真核生物中,随后在几个真核生物谱系中多次丢失的可能性。
This study characterizes the KAP protein family - a newly identified sub-group of the P-loop NTPases, which have transmembrane helices inserted into the P-loop NTPase domain. Their unusual phyletic distribution suggests KAP proteins were transferred from bacteria to animals by horizontal gene transfer. Recent sequence-structure studies on P-loop-fold NTPases have substantially advanced the existing understanding of their evolution and functional diversity. These studies provide a framework for characterization of novel lineages within this fold and prediction of their functional properties. Using sequence profile searches and homology-based structure prediction, we have identified a previously uncharacterized family of P-loop NTPases, which includes the neuronal membrane protein and receptor tyrosine kinase substrate Kidins220/ARMS, which is conserved in animals, the F-plasmid PifA protein involved in phage T7 exclusion, and several uncharacterized bacterial proteins. We refer to these (predicted) NTPases as the KAP family, after Kidins220/ARMS and PifA. The KAP family NTPases are sporadically distributed across a wide phylogenetic range in bacteria but among the eukaryotes are represented only in animals. Many of the prokaryotic KAP NTPases are encoded in plasmids and tend to undergo disruption to form pseudogenes. A unique feature of all eukaryotic and certain bacterial KAP NTPases is the presence of two or four transmembrane helices inserted into the P-loop NTPase domain. These transmembrane helices anchor KAP NTPases in the membrane such that the P-loop domain is located on the intracellular side. We show that the KAP family belongs to the same major division of the P-loop NTPase fold with the AAA+, ABC, RecA-like, VirD4-like, PilT-like, and AP/NACHT-like NTPase classes. In addition to the KAP family, we identified another small family of predicted bacterial NTPases, with two transmembrane helices inserted into the P-loop domain. This family is not specifically related to the KAP NTPases, suggesting independent acquisition of the transmembrane helices. We predict that KAP family NTPases function principally in the NTP-dependent dynamics of protein complexes, especially those associated with the intracellular surface of cell membranes. Animal KAP NTPases, including Kidins220/ARMS, are likely to function as NTP-dependent regulators of the assembly of membrane-associated signaling complexes involved in neurite growth and development. One possible function of the prokaryotic KAP NTPases might be in the exclusion of selfish replicons, such as viruses, from the host cells. Phylogenetic analysis and phyletic patterns suggest that the common ancestor of the animals acquired a KAP NTPase via lateral transfer from bacteria. However, an earlier transfer into eukaryotes followed by multiple losses in several eukaryotic lineages cannot be ruled out.
DOI: 10.1093/nar/17.12.4713
发表时间: 1989-06-26
影响因子: 14.9
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期刊: PROTEINS-STRUCTURE FUNCTION AND GENETICS
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影响因子: 13.8
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DOI: 10.1128/jvi.17.1.94-105.1976
发表时间: 1976-01-01
影响因子: 5.4
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发表时间: 2002-07-01
影响因子: 2.9
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