Light-dependent gene regulation by a coenzyme B12-based photoreceptor
Light-dependent gene regulation by a coenzyme B12-based photoreceptor
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DOI：
10.1073/pnas.1018972108
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发表时间：
2011-05-03
影响因子：
11.1
通讯作者：
Elias-Arnanz, Montserrat
中科院分区：
文献类型：
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作者：
Manuel Ortiz-Guerrero, Juan;Carmen Polanco, Maria;Elias-Arnanz, Montserrat
钴胺素 (B-12) 通常充当酶辅助因子，但也可以通过基于 RNA 的核糖开关调节基因表达。然而，通过蛋白质因子进行的 B-12 定向基因调控机制仍然难以捉摸。最近，我们报道了两种旁系同源转录抑制子对黄色粘球菌中光诱导启动子的下调，其中一种是 CarH，另一种是 CarA，绝对需要 B-12 才能发挥活性，尽管两者都具有典型的 B-12 结合基序。尚不清楚这种显着差异背后的原因、所使用的具体钴胺素是什么以及它如何发挥作用。在这里，我们证明辅酶 B-12（5'-脱氧腺苷钴胺素，AdoB(12)）在黑暗和光照下特异性决定 CarH 功能。在黑暗中，AdoB(12) 与包含 B-12 结合基序的自主结构域的结合会引发阻遏物寡聚化，增强操纵子结合并阻断转录。 AdoB(12) 吸收的不同波长的光通过光解结合的 AdoB(12) 来分解活性阻遏蛋白寡聚体，并削弱阻遏蛋白-操纵子结合以允许转录。相比之下，AdoB(12) 既不改变 CarA 寡聚化，也不改变操纵子结合，从而解释了其不依赖于 B-12 的活性。我们的研究结果揭示了 AdoB(12) 的一个功能方面，它作为一种独特的光感受器蛋白类的发色团，在光依赖性基因调控中发挥作用。微生物基因组中功能未知的类似蛋白质的普遍存在表明，这种独特的基于 B-12 的光调节分子机制可能广泛存在于细菌中。
Cobalamin (B-12) typically functions as an enzyme cofactor but can also regulate gene expression via RNA-based riboswitches. B-12-directed gene regulatory mechanisms via protein factors have, however, remained elusive. Recently, we reported down-regulation of a light-inducible promoter in the bacterium Myxococcus xanthus by two paralogous transcriptional repressors, of which one, CarH, but not the other, CarA, absolutely requires B-12 for activity even though both have a canonical B-12-binding motif. Unanswered were what underlies this striking difference, what is the specific cobalamin used, and how it acts. Here, we show that coenzyme B-12 (5'-deoxyadenosylcobalamin, AdoB(12)), specifically dictates CarH function in the dark and on exposure to light. In the dark, AdoB(12)-binding to the autonomous domain containing the B-12-binding motif foments repressor oligomerization, enhances operator binding, and blocks transcription. Light, at various wavelengths at which AdoB(12) absorbs, dismantles active repressor oligomers by photolysing the bound AdoB(12) and weakens repressor-operator binding to allow transcription. By contrast, AdoB(12) alters neither CarA oligomerization nor operator binding, thus accounting for its B-12-independent activity. Our findings unveil a functional facet of AdoB(12) whereby it serves as the chromophore of a unique photoreceptor protein class acting in light-dependent gene regulation. The prevalence of similar proteins of unknown function in microbial genomes suggests that this distinct B-12-based molecular mechanism for photoregulation may be widespread in bacteria.