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腾讯登录PNAS：发现细菌质量控制的分子机制
| 导读 | 近日，刊登在国际著名杂志<em>PNAS</em>上的一篇报道指出，在双精氨酸分泌系统（TAT）中发现了质量控制的机制，双精氨酸分泌系统是植物、细菌和古细菌的一种蛋白质输出途径。这种跨膜的蛋白质运输是一种基本的生命过程，理解TAT途径如何工作对于理解细菌如何产生对抗生素耐药非常重要。
TAT途径非常值得注意，不像其它过程，TAT过程中，蛋白质是以紧密折叠的形式经过细胞... |
近日，刊登在国际著名杂志<em>PNAS</em>上的一篇报道指出，在双精氨酸分泌系统（TAT）中发现了质量控制的机制，双精氨酸分泌系统是植物、细菌和古细菌的一种蛋白质输出途径。这种跨膜的蛋白质运输是一种基本的生命过程，理解TAT途径如何工作对于理解细菌如何产生对抗生素耐药非常重要。
TAT途径非常值得注意，不像其它过程，TAT过程中，蛋白质是以紧密折叠的形式经过细胞膜的。这种途径允许蛋白质合适地折叠，错误折叠将不会被允许通过。在TAT出口中使用遗传选择的方法，研究者就可以分离出一种突变（TAT机器中的抑制子），来使得细菌即便输出错误蛋白的时候也使得细菌存活。细菌的这种能力归咎于他们外排错误折叠蛋白的能力。正常细菌是不行的。研究者提出了TAT机器直接调节蛋白质输出的证据。
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他们推测，TAT机器包含了一些组分可以感知是否蛋白质被正确折叠，并且区别蛋白石处于折叠还是未折叠的状态。TAT途径调节蛋白质的质量为生物技术公司开发合适的抗体提供了基础条件。数年前，研究者Delisa关于TAT路径的研究成果就为生物技术公司开发治疗阿尔兹海默症的药物提供了思路。
所有这种机制，包括质量控制特征都是一种生物技术元素，应当被用于寻找抗体，使其特异性的结合至其靶点上。相关研究由国立卫生研究院支持。
编译自：<a title="" href="http://phys.org/news/2012-08-quality-control-mechanism-bacteria.html" target="_blank">Quality-control mechanism found in bacteria</a>
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<a title="" href="http://dx.doi.org/doi:10.1073/pnas.1210140109" target="_blank">doi:10.1073/pnas.1210140109</a>
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<br/><strong>Twin-arginine translocase mutations that suppress folding quality control and permit export of misfolded substrate proteins</strong><br/>
Mark A. Roccoa, Dujduan Waraho-Zhmayevb,c, and Matthew P. DeLisaa,b,1
The bacterial twin-arginine translocation (Tat) pathway facilitates the transport of correctly folded proteins across the tightly sealed cytoplasmic membrane. Here, we report the isolation and characterization of suppressor mutations in the Tat translocase that allow export of misfolded proteins, which form structures that are not normally tolerated by the wild-type translocase. Selection of suppressors was enabled by a genetic assay that effectively linked in vivo folding and stability of a test protein with Tat export efficiency of a selectable marker protein, namely TEM-1 β-lactamase. By using a test protein named α3B—a designed three-helix-bundle protein that forms collapsed, stable molten globules but lacks a uniquely folded structure—translocase mutants that rescued export of this protein were readily identified. Each mutant translocase still efficiently exported folded substrate proteins, indicating that the substrate specificity of suppressors was relaxed but not strictly altered. A subset of the suppressors could also export other misfolded proteins, such as the aggregation-prone α3A protein and reduced alkaline phosphatase. Importantly, the isolation of genetic suppressors that inactivate the Tat quality-control mechanism provides direct evidence for the participation of the Tat translocase in structural proofreading of substrate proteins and reveals epitopes in the translocase that are important for this process.
<br/>来源：生物谷
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TAT途径非常值得注意，不像其它过程，TAT过程中，蛋白质是以紧密折叠的形式经过细胞膜的。这种途径允许蛋白质合适地折叠，错误折叠将不会被允许通过。在TAT出口中使用遗传选择的方法，研究者就可以分离出一种突变（TAT机器中的抑制子），来使得细菌即便输出错误蛋白的时候也使得细菌存活。细菌的这种能力归咎于他们外排错误折叠蛋白的能力。正常细菌是不行的。研究者提出了TAT机器直接调节蛋白质输出的证据。
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他们推测，TAT机器包含了一些组分可以感知是否蛋白质被正确折叠，并且区别蛋白石处于折叠还是未折叠的状态。TAT途径调节蛋白质的质量为生物技术公司开发合适的抗体提供了基础条件。数年前，研究者Delisa关于TAT路径的研究成果就为生物技术公司开发治疗阿尔兹海默症的药物提供了思路。
所有这种机制，包括质量控制特征都是一种生物技术元素，应当被用于寻找抗体，使其特异性的结合至其靶点上。相关研究由国立卫生研究院支持。
编译自：<a title="" href="http://phys.org/news/2012-08-quality-control-mechanism-bacteria.html" target="_blank">Quality-control mechanism found in bacteria</a>
<div id="ztload">
<div> </div>
<div>
<div>
<img src="http://www.bioon.com/biology/UploadFiles/201208/2012080523230634.jpg" alt="" width="113" height="149" border="0" />
<a title="" href="http://dx.doi.org/doi:10.1073/pnas.1210140109" target="_blank">doi:10.1073/pnas.1210140109</a>
PMC:
PMID:
</div>
<div>
<br/><strong>Twin-arginine translocase mutations that suppress folding quality control and permit export of misfolded substrate proteins</strong><br/>
Mark A. Roccoa, Dujduan Waraho-Zhmayevb,c, and Matthew P. DeLisaa,b,1
The bacterial twin-arginine translocation (Tat) pathway facilitates the transport of correctly folded proteins across the tightly sealed cytoplasmic membrane. Here, we report the isolation and characterization of suppressor mutations in the Tat translocase that allow export of misfolded proteins, which form structures that are not normally tolerated by the wild-type translocase. Selection of suppressors was enabled by a genetic assay that effectively linked in vivo folding and stability of a test protein with Tat export efficiency of a selectable marker protein, namely TEM-1 β-lactamase. By using a test protein named α3B—a designed three-helix-bundle protein that forms collapsed, stable molten globules but lacks a uniquely folded structure—translocase mutants that rescued export of this protein were readily identified. Each mutant translocase still efficiently exported folded substrate proteins, indicating that the substrate specificity of suppressors was relaxed but not strictly altered. A subset of the suppressors could also export other misfolded proteins, such as the aggregation-prone α3A protein and reduced alkaline phosphatase. Importantly, the isolation of genetic suppressors that inactivate the Tat quality-control mechanism provides direct evidence for the participation of the Tat translocase in structural proofreading of substrate proteins and reveals epitopes in the translocase that are important for this process.
<br/>来源：生物谷
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