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基于计算机模拟、体外和体内研究对小鼠鸟苷结合蛋白(GBP)同源簇的分析。

Analyses of murine GBP homology clusters based on in silico, in vitro and in vivo studies.

作者信息

Kresse Alexandra, Konermann Carolin, Degrandi Daniel, Beuter-Gunia Cornelia, Wuerthner Jan, Pfeffer Klaus, Beer Sandra

机构信息

Institute of Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University, Universitaetsstrasse 1, 40225 Duesseldorf, Germany.

出版信息

BMC Genomics. 2008 Apr 10;9:158. doi: 10.1186/1471-2164-9-158.

Abstract

The interactions between pathogens and hosts lead to a massive upregulation of antimicrobial host effector molecules. Among these, the 65 kDa guanylate binding proteins (GBPs) are interesting candidates as intricate components of the host effector molecule repertoire. Members of the GBP family are highly conserved in vertebrates. Previous reports indicate an antiviral activity of human GBP1 (hGBP1) and murine GBP2 (mGBP2). We recently demonstrated that distinct murine GBP (mGBP) family members are highly upregulated upon Toxoplasma gondii infection and localize around the intracellular protozoa T. gondii. Moreover, we characterised five new mGBP family members within the murine 65 kDa GBP family. Here, we identified a new mGBP locus named mGbp11. Based on bacterial artificial chromosome (BAC), expressed sequence tag (EST), and RT-PCR analyses this study provides a detailed insight into the genomic localization and organization of the mGBPs. These analyses revealed a 166-kb spanning region on chromosome 3 harboring five transcribed mGBPs (mGbp1, mGbp2, mGbp3, mGbp5, and mGbp7) and one pseudogene (pseudomGbp1), as well as a 332-kb spanning region on chromosome 5 consisting of six transcribed mGBPs (mGbp4, mGbp6, mGbp8, mGbp9, mGbp10, and mGbp11), and one pseudogene (pseudomgbp2). Besides the strikingly high homology of 65% to 98% within the coding sequences, the mGBPs on chromosome 5 cluster also exhibit a highly homologous exon-intron structure whereas the mGBP on chromosome 3 reveals a more divergent exon-intron structure. This study details the comprehensive genomic organization of mGBPs and suggests that a continuously changing microbial environment has exerted evolutionary pressure on this gene family leading to multiple gene amplifications. A list of links for this article can be found in the Availability and requirements section.

摘要

病原体与宿主之间的相互作用导致宿主抗菌效应分子大量上调。其中,65 kDa鸟苷酸结合蛋白(GBP)作为宿主效应分子库的复杂组成部分,是有趣的候选分子。GBP家族成员在脊椎动物中高度保守。先前的报道表明人GBP1(hGBP1)和鼠GBP2(mGBP2)具有抗病毒活性。我们最近证明,在刚地弓形虫感染后,不同的鼠GBP(mGBP)家族成员高度上调,并定位于细胞内原生动物刚地弓形虫周围。此外,我们在鼠65 kDa GBP家族中鉴定了五个新的mGBP家族成员。在这里,我们鉴定了一个名为mGbp11的新mGBP基因座。基于细菌人工染色体(BAC)、表达序列标签(EST)和RT-PCR分析,本研究详细深入地了解了mGBP的基因组定位和组织。这些分析揭示了3号染色体上一个跨度为166 kb的区域,包含五个转录的mGBP(mGbp1、mGbp2、mGbp3、mGbp5和mGbp7)和一个假基因(假mGbp1),以及5号染色体上一个跨度为332 kb的区域,由六个转录的mGBP(mGbp4、mGbp6、mGbp8、mGbp9、mGbp10和mGbp11)和一个假基因(假mgbp2)组成。除了编码序列中65%至98%的惊人高同源性外,5号染色体上的mGBP簇还表现出高度同源的外显子-内含子结构,而3号染色体上的mGBP则显示出更具差异的外显子-内含子结构。本研究详细阐述了mGBP的全面基因组组织,并表明不断变化的微生物环境对该基因家族施加了进化压力,导致了多个基因扩增。本文的链接列表可在“可用性和要求”部分找到。

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