Comparative analysis of HOG pathway proteins to generate hypotheses for functional analysis

Comparative analysis of HOG pathway proteins to generate hypotheses for functional analysis
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DOI:
10.1007/s00294-005-0039-9
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发表时间:
2006-03-01
期刊:
影响因子:
2.5
通讯作者:
Hohmann, S
Hohmann, S
中科院分区:
生物学3区
文献类型:
--
作者:
Krantz, M;Becit, E;Hohmann, S

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比较基因组学允许比较在不同生物体中执行可能相同功能的不同蛋白质。与旁系同源物相比,根据定义,直向同源物执行相同的功能并与相同的伙伴相互作用,因此,应该在所有这些特性中表现出保守性。我们采用 20 个真菌基因组来分析酿酒酵母高渗透压甘油信号通路的关键成分。所检查的蛋白质包括完整的磷酸转移模块、MAP 激酶、两种支架蛋白(其中之一也是 MAPKK)和两种转录因子。序列比对、结构域结构和大小分析,结合文献中丰富的信息,使我们能够探索以前的结构和功能研究,并为未来的实验研究提出假设。尽管某些域在真菌物种中过于保守,无法进行有意义的比较研究,但其他域(例如相互作用域)可以在密切相关的物种中进行研究。此外,在此类比较研究中可以鉴定蛋白质修饰的推定功能相关位点。我们提供了几个相关的例子,并提出了一些以前未表征的、在渗透传感和信号转导中具有潜在功能意义的域。我们建议真菌中的任何功能性蛋白质分析都应利用真菌基因组序列提供的独特资源。
Comparative genomics allows comparison of different proteins that execute presumably identical functions in different organisms. In contrast to paralogues, orthologues per definition perform the same function and interact with the same partners and, consequently, should display conservation in all these properties. We have employed 20 fungal genomes to analyse key components of the high osmolarity glycerol signalling pathway of Saccharomyces cerevisiae. Among the proteins scrutinised are a complete phosphotransfer module, a MAP kinase, two scaffold proteins, one of which is also a MAPKK, and two transcription factors. Sequence alignments, domain structure and size analysis, combined with the rich information available in the literature, allowed us to probe previous structural and functional studies and to generate hypotheses for future experimental studies. Although certain domains are too highly conserved across fungal species for meaningful comparative studies, others, like interaction domains, can be studied in closely related species. Moreover, putative functionally relevant sites for protein modifications can be identified in such comparative studies. We provide several relevant examples and present a number of previously un(der)characterised domains of potential functional significance in osmosensing and signal transduction. We propose that any functional protein analysis in fungi should make use of the unique resource that fungal genome sequences offer.