Structural studies of human glioma pathogenesis-related protein 1.

Asojo OA; Koski RA; Bonafe N

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Structural studies of human glioma pathogenesis-related protein 1.

机译：人类神经胶质瘤的结构的研究pathogenesis-related蛋白质1。

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Human glioma pathogenesis-related protein 1 (GLIPR1) is a membrane protein that is highly upregulated in brain cancers but is barely detectable in normal brain tissue. GLIPR1 is composed of a signal peptide that directs its secretion, a conserved cysteine-rich CAP (cysteine-rich secretory proteins, antigen 5 and pathogenesis-related 1 proteins) domain and a transmembrane domain. GLIPR1 is currently being investigated as a candidate for prostate cancer gene therapy and for glioblastoma targeted therapy. Crystal structures of a truncated soluble domain of the human GLIPR1 protein (sGLIPR1) solved by molecular replacement using a truncated polyalanine search model of the CAP domain of stecrisp, a snake-venom cysteine-rich secretory protein (CRISP), are presented. The correct molecular-replacement solution could only be obtained by removing all loops from the search model. The native structure was refined to 1.85 A resolution and that of a Zn2+ complex was refined to 2.2 A resolution. The latter structure revealed that the putative binding cavity coordinates Zn2+ similarly to snake-venom CRISPs, which are involved in Zn2+-dependent mechanisms of inflammatory modulation. Both sGLIPR1 structures have extensive flexible loop/turn regions and unique charge distributions that were not observed in any of the previously reported CAP protein structures. A model is also proposed for the structure of full-length membrane-bound GLIPR1.

机译：人类神经胶质瘤pathogenesis-related蛋白质1(GLIPR1)是一种高度的膜蛋白调节大脑癌症,但几乎没有检测在正常脑组织。由一个信号肽引导它分泌,守恒cysteine-rich帽(cysteine-rich分泌蛋白质,抗原5pathogenesis-related 1蛋白质)域和一个跨膜域。调查作为前列腺癌的候选人基因疗法和胶质母细胞瘤的目标治疗。可溶性域的人类GLIPR1蛋白质(sGLIPR1)解决分子替换使用截断polyalanine搜索模型的帽子域stecrisp,蛇毒cysteine-rich分泌蛋白(脆)。正确molecular-replacement只能解决方案通过删除所有循环搜索模型。分辨率和Zn2 +复杂的精制2.2解决方案。透露,假定的绑定腔坐标Zn2 +类似蛇毒薯片,这是参与Zn2 +端依赖机制炎症的调制。结构广泛灵活循环/地区和独特的电荷分布没有观察到任何报道限制蛋白质结构。为完整的膜结合的结构

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来源
《Acta crystallographica.Section D. Biological crystallography》 |2011年第10期|847-855|共9页
作者
Asojo OA; Koski RA; Bonafe N;
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作者单位

Department of Pathology and Microbiology, College of Medicine, Nebraska Medical Center, Omaha, NE 68198-6495, USA.;

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正文语种英语
中图分类化学;
关键词
GLIPR1 gene; STRUCTURAL STUDY; Brain CancerSignal Peptidescancer gene therapyMembrane ProteinsGliomaLipoblastoma;

机译：大脑CancerSignal GLIPR1基因;结构研究Peptidescancer基因therapyMembrane;

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Structural studies of human glioma pathogenesis-related protein 1.

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