Evolutionary Analysis of Functional Divergence among Chemokine Receptors, Decoy Receptors, and Viral Receptors.
Evolutionary Analysis of Functional Divergence among Chemokine Receptors, Decoy Receptors, and Viral Receptors.
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DOI：
10.3389/fmicb.2012.00264
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发表时间：
2012
影响因子：
5.2
通讯作者：
Toh H
中科院分区：
文献类型：
--
作者：
Daiyasu H;Nemoto W;Toh H
趋化因子受体（CKRs）在炎症反应和脊椎动物体内平衡中起作用。诱饵受体和病毒受体是两种类型的CKR同源物，其功能与典型的CKR相比有所改变。诱饵受体能够结合配体而不发出信号。另一方面，病毒受体在没有配体的情况下表现出组成型信号。我们检查了与功能差异相关的位点。首先，根据分子系统发育分析，将诱饵和病毒受体分别分为五组。然后构建了每组与ckr之间的多个氨基酸序列比对。利用各比对位点的Kullback-Leibler （KL）信息值评价各组与ckr之间氨基酸组成的差异。KL信息值被认为反映了该地点功能约束的差异。选择KL信息值前5%的位点，并将其映射到CKR的结构上。与诱饵受体组的比较显示，检测位点偏向于细胞内侧。相比之下，从与病毒受体组的比较中检测到的位点在细胞外和细胞内两侧都发现。在病毒受体组的分析中，与诱饵受体组相比，在配体结合袋中发现了更多的位点。部分检测到的位点位于GPCR基序中。例如，诱饵受体的DRY基序经常被降解，尽管病毒受体的基序基本是保守的。对病毒受体组的观察表明，袋区约束较松散，细胞内侧的位点与诱饵受体的位点不同，这可能与病毒受体的组成信号活性有关。
Chemokine receptors (CKRs) function in the inflammatory response and in vertebrate homeostasis. Decoy and viral receptors are two types of CKR homologs with modified functions from those of the typical CKRs. The decoy receptors are able to bind ligands without signaling. On the other hand, the viral receptors show constitutive signaling without ligands. We examined the sites related to the functional difference. At first, the decoy and viral receptors were each classified into five groups, based on the molecular phylogenetic analysis. A multiple amino acid sequence alignment between each group and the CKRs was then constructed. The difference in the amino acid composition between the group and the CKRs was evaluated as the Kullback–Leibler (KL) information value at each alignment site. The KL information value is considered to reflect the difference in the functional constraints at the site. The sites with the top 5% of KL information values were selected and mapped on the structure of a CKR. The comparisons with decoy receptor groups revealed that the detected sites were biased on the intracellular side. In contrast, the sites detected from the comparisons with viral receptor groups were found on both the extracellular and intracellular sides. More sites were found in the ligand binding pocket in the analyses of the viral receptor groups, as compared to the decoy receptor groups. Some of the detected sites were located in the GPCR motifs. For example, the DRY motif of the decoy receptors was often degraded, although the motif of the viral receptors was basically conserved. The observations for the viral receptor groups suggested that the constraints in the pocket region are loose and that the sites on the intracellular side are different from those for the decoy receptors, which may be related to the constitutive signaling activity of the viral receptors.
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DOI：
10.1093/bioinformatics/8.3.275
发表时间：
1992-06-01
期刊：
COMPUTER APPLICATIONS IN THE BIOSCIENCES
影响因子：
--
作者：
JONES, DT;TAYLOR, WR;THORNTON, JM
通讯作者：
THORNTON, JM
影响因子：
10.7
作者：
Gu, X
通讯作者：
Gu, X
影响因子：
5.4
作者：
Camarda, G;Spinetti, G;Napolitano, M
通讯作者：
Napolitano, M
影响因子：
4.8
作者：
Arias, DA;Navenot, JM;Peiper, SC
通讯作者：
Peiper, SC
影响因子：
5.6
作者：
Hannenhalli, SS;Russell, RB
通讯作者：
Russell, RB