The retinal specific CD147 Ig0 domain: from molecular structure to biological activity.
The retinal specific CD147 Ig0 domain: from molecular structure to biological activity.
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DOI：
10.1016/j.jmb.2011.04.060
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发表时间：
2011-08-05
影响因子：
5.6
通讯作者：
Eisenmesser EZ
中科院分区：
文献类型：
--
作者：
Redzic JS;Armstrong GS;Isern NG;Jones DN;Kieft JS;Eisenmesser EZ
CD147是一种I型跨膜蛋白，与炎症性疾病、癌症进展有关，多种人类病原体利用CD147进行有效感染。在一些癌症中，CD147的表达如此之高，以至于现在它被用作预后标志。CD147的两种主要亚型与癌症进展相关，它们的免疫球蛋白(Ig)样结构域的数量不同。这些基因包括CD147IG1-IG2，它在大多数组织中普遍表达，以及CD147IG0-IG1-IG2，它是视网膜特异性的，与视网膜母细胞瘤有关。然而，尽管CD147 Ig0结构域在视网膜母细胞瘤中具有潜在的作用，但人们对其知之甚少。我们提出了人CD147 Ig0结构域的第一个晶体结构，并表明CD147 Ig0结构域是一种具有I型结构域结构的晶体二聚体，该结构域在溶液中保持不变。此外，我们利用我们的结构数据和诱变技术，在几个模型细胞系中探索了含有CD147的蛋白质在几个模型细胞系中的生物活性。我们的发现表明，CD147 Ig0结构域是IL-6的有效刺激因子，并提示CD147 Ig0结构域具有不同于其他CD147类Ig结构域的受体CD147 IG1-IG2。最后，我们证明了CD147Ig0二聚体是活性所需的功能单位，可以被单点突变破坏。
CD147 is a type I transmembrane protein that is involved in inflammatory diseases, cancer progression, and multiple human pathogens utilize CD147 for efficient infection. In several cancers, CD147 expression is so high that it is now used as a prognostic marker. The two primary isoforms of CD147 that are related to cancer progression have been identified, differing in their number of immunoglobulin (Ig)-like domains. These include CD147 Ig1-Ig2 that is ubiquitously expressed in most tissues and CD147 Ig0-Ig1-Ig2 that is retinal specific and implicated in retinoblastoma. However, little is known in regard to the retinal specific CD147 Ig0 domain despite its potential role in retinoblastoma. We present the first crystal structure of the human CD147 Ig0 domain and show that the CD147 Ig0 domain is a crystallographic dimer with an I-type domain structure, which is maintained in solution. Furthermore, we have utilized our structural data together with mutagenesis to probe the biological activity of CD147-containing proteins both with and without the CD147 Ig0 domain within several model cell lines. Our findings reveal that the CD147 Ig0 domain is a potent stimulator of interleukin-6 and suggest that the CD147 Ig0 domain has its own receptor distinct from that of the other CD147 Ig-like domains, CD147 Ig1-Ig2. Finally, we show that the CD147 Ig0 dimer is the functional unit required for activity and can be disrupted by a single point mutation.
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影响因子：
4.8
作者：
Langnaese, K;Beesley, PW;Gundelfinger, ED
通讯作者：
Gundelfinger, ED
影响因子：
7.5
作者：
Castellana, Donatello;Toti, Florence;Freyssinet, Jean-Marie
通讯作者：
Freyssinet, Jean-Marie
影响因子：
3.4
作者：
JAFFE, GJ;ROBERTS, WL;CIANCIOLO, GJ
通讯作者：
CIANCIOLO, GJ
影响因子：
5.6
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
通讯作者：
Elsenmesser, Elan Zohar
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH