加快“指尖”，发现二十年的蛋白质信息在一个地方

在霍普金斯大学的研究人员利用一种新技术，是蛋白质的组成确定几乎所有的化学变化，通过添加磷酸盐制造人类细胞中的蛋白质使自然。

霍普金斯的团队加入其所谓的磷酸化事件清单编制人名单和创建Web phosphomotif仪-一个公开的数据库，帮助加速了世界各地的研究人员的工作。

“发现在同一时间这么多的是一个巨大的进步，”akhilesh Pandey说，医学博士，博士，副教授在遗传医学麦库西克-内森斯研究所霍普金斯。“磷酸化是控制我们的细胞的蛋白质工厂，化学反应的本质，和磷酸化的消失有牵连的几种疾病。同时研究多个phosphorlyation能力将帮助我们了解这些疾病-包括癌症早。

“我们这里是一个可搜索的目录很多工作约20年，”Pandey。所有新发现的蛋白质改变的报告发表于2月13日的问题国家科学院学报，数据库的报告出现在3月刊上自然生物技术。

Pandey’s team used electron transfer dissociation (ETD) tandem mass spectrometry， a technology that breaks apart proteins into small fragments， separates them by size and identifies the fragments based on their mass - their size and weight。 The process improves on previous techniques by breaking up proteins more gently and keeping chemical modifications like phosphorylation intact。 Previous spectrometry methods were “just too rough” on the delicate protein alterations and sheared them right off， he says。  “We had to guess where they might be and nobody wants to chase false leads based on wrong guesses。”

Pandey says the original goal of the research was to identify accurately as many protein changes as possible using the new technology。 “But to see how well we measured up， we had to compare our findings to what already was published， and there was just no clean， easy way of doing that because there were reports all over the place。

“That’s when we decided to go through and consolidate just about everything on phosphorylation that was out there。”

Working with human kidney cells， the researchers fished out the thousands of different proteins and analyzed them by ETD， resulting in a net total of 1，435 phosphorylations。 Comparing these 1，435 to the 20 years’ of published data， they discovered that about 80 percent of what they found never had been reported。

The team then constructed an online search tool， PhosphoMotif Finder， which was incorporated into their previously established Human Protein Reference Database。 Human Protein Reference Database now contains about 16，000 phosphorylation sites described in the literature and the PhosphoMotif Finder tool allows any researcher to find potential phosphorylation sites in any protein of interest。

“The power of this technique is not just in the numbers，” says Pandey。 “Rather， we’ve found what you might call new information about old proteins， and we hope the new data will help researchers study their favorite proteins in greater depth。 After all， there’s no sense in reinventing the wheel。”

Pandey and his team now are curious about other chemical modifications of proteins， which are the “business-end” products of our genes。  “There is evidence of other， more fragile modifications that until now no one has been able to get a handle on because they’re way too hard to work with。 Now we have the tools to probe further，” he says。

The research was funded by the U。S。 Public Health Service， Canadian Institute of Health Research， National Institutes of Health， National Heart， Lung and Blood Institute and the National Multiple Sclerosis Society。

作者在国家科学院学报 paper are Henrik Molina and Pandey， of Hopkins; Suresh Mathivanan of the Institute of Bioinformatics in Bangalore， India; and David Horn and Ning Tang of Agilent Technologies in Santa Clara， Calif。 Authors on the 自然生物技术 paper are Ramars Amanchy， Balamurugan Periaswamy， Suresh Mathivanan， Raghunath Reddy， and Pandey， all of Hopkins; and Sudhir Gopal Tattikota of the Institute of Bioinformatics in Bangalore， India。

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