Solution characterization of the extracellular region of CD147 and its interaction with its enzyme ligand cyclophilin A.
Solution characterization of the extracellular region of CD147 and its interaction with its enzyme ligand cyclophilin A.
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DOI：
10.1016/j.jmb.2009.05.080
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发表时间：
2009-08-21
影响因子：
5.6
通讯作者：
Elsenmesser, Elan Zohar
中科院分区：
文献类型：
--
作者：
Schlegel, Jennifer;Redzic, Jasmina S.;Porter, Christopher C.;Yurchenko, Vyacheslav;Bukrinsky, Michael;Labeikovsky, Wladimir;Armstrong, Geoffrey S.;Zhang, Fengli;Isern, Nancy G.;DeGregori, James;Hodges, Robert;Elsenmesser, Elan Zohar
CD 147受体通过刺激几种蛋白质家族的表达并作为细胞外亲环素的受体在许多疾病中起着不可或缺的作用;然而，无论是CD 147还是其与亲环素配体的相互作用都没有在溶液中得到很好的表征。CD 147是一种独特的蛋白质，因为它可以在细胞膜上发挥作用，也可以在从细胞释放后继续保持活性。因此，CD 147受体通过至少两种机制发挥作用，包括亲环蛋白非依赖性和亲环蛋白依赖性作用模式。关于CD 147亲环蛋白非依赖性活性，认为CD 147亲环性相互作用是其活性的基础。关于CD 147亲环蛋白依赖性活性，亲环蛋白/CD 147相互作用可能代表一种新的信号传导方式，因为亲环蛋白也是肽基脯氨酰异构酶。然而，在亲环蛋白/CD 147复合物中尚未显示催化作用的直接证据。在这份报告中，我们已经通过生物化学方法，包括凝胶过滤和天然凝胶分析，以及直接通过多种NMR方法的特点的两个最流行的CD 147细胞外亚型的溶液行为。所有的方法表明，细胞外免疫球蛋白样结构域在溶液中是单体的，因此，表明在体内的CD 147嗜同性相互作用是通过其他合作伙伴介导的。此外，使用多种NMR技术，我们已经确定并表征了CD 147上的亲环素靶位点，并首次表明CD 147也是其主要亲环素酶配体亲环素A的底物。
The CD147 receptor plays an integral role in numerous diseases by stimulating the expression of several protein families and serving as the receptor for extracellular cyclophilins; however, neither CD147 nor its interactions with its cyclophilin ligands have been well characterized in solution. CD147 is a unique protein in that it can function both at the cell membrane and after being released from cells where it continues to retain activity. Thus, the CD147 receptor functions through at least two mechanisms that include both cyclophilin-independent and cyclophilin-dependent modes of action. In regard to CD147 cyclophilin-independent activity, CD147 homophilic interactions are thought to underlie its activity. In regard to CD147 cyclophilin-dependent activity, cyclophilin/CD147 interactions may represent a novel means of signaling since cyclophilins are also peptidyl–prolyl isomerases. However, direct evidence of catalysis has not been shown within the cyclophilin/CD147 complex. In this report, we have characterized the solution behavior of the two most prevalent CD147 extracellular isoforms through biochemical methods that include gel-filtration and native gel analysis as well as directly through multiple NMR methods. All methods indicate that the extracellular immunoglobulin-like domains are monomeric in solution and, thus, suggest that CD147 homophilic interactions in vivo are mediated through other partners. Additionally, using multiple NMR techniques, we have identified and characterized the cyclophilin target site on CD147 and have shown for the first time that CD147 is also a substrate of its primary cyclophilin enzyme ligand, cyclophilin A.
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影响因子：
2.7
作者：
d'Auvergne EJ;Gooley PR
通讯作者：
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影响因子：
4.4
作者：
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通讯作者：
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作者：
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通讯作者：
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DOI：
10.1016/j.biocel.2006.03.019
发表时间：
2006-01-01
影响因子：
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作者：
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通讯作者：
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DOI：
10.1084/jem.185.5.975
发表时间：
1997-03-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Billich A;Winkler G;Aschauer H;Rot A;Peichl P
通讯作者：
Peichl P