Crystal structures of the SAM-III/S(MK) riboswitch reveal the SAM-dependent translation inhibition mechanism.

Crystal structures of the SAM-III/S(MK) riboswitch reveal the SAM-dependent translation inhibition mechanism.
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DOI:
10.1038/nsmb.1494
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发表时间:
2008-10
影响因子:
16.8
通讯作者:
--
中科院分区:
生物学1区
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--
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已鉴定出三类不同类型的S-腺苷-L-蛋氨酸响应核糖开关,它们在转录抑制或翻译抑制水平上调节细菌基因的表达。SMK盒(SAM-III)翻译核糖开关在乳杆菌的SAM合成酶基因中已被发现。在这里,我们报道了粪肠球菌SMK盒核糖开关的2.2°晶体结构。Y型核糖开关将其保守的核苷酸组织在一个三向连接周围,用于识别SAM。Shine-Dalgarno序列也直接参与SAM的识别,该序列通过碱基配对与SAM结合的反Shine-Dalgarno序列隔离。核糖开关与SAM的腺苷和硫部分发生广泛的相互作用,但似乎不识别蛋氨酸部分的尾部。我们捕获了SMK盒核糖开关采样近同源配体S-腺苷-L-同型半胱氨酸的结构快照,发现其中的同源配体采用了另一种构象,未能进行几个关键的相互作用。
Three distinct classes of S-adenosyl-l-methionine (SAM)-responsive riboswitches have been identified that regulate bacterial gene expression at the levels of transcription attenuation or translation inhibition. The SMK box (SAM-III) translational riboswitch has been identified in the SAM synthetase gene in members of the Lactobacillales. Here we report the 2.2-Å crystal structure of the Enterococcus faecalis SMK box riboswitch. The Y-shaped riboswitch organizes its conserved nucleotides around a three-way junction for SAM recognition. The Shine-Dalgarno sequence, which is sequestered by base-pairing with the anti–Shine-Dalgarno sequence in response to SAM binding, also directly participates in SAM recognition. The riboswitch makes extensive interactions with the adenosine and sulfonium moieties of SAM but does not appear to recognize the tail of the methionine moiety. We captured a structural snapshot of the SMK box riboswitch sampling the near-cognate ligand S-adenosyl-l-homocysteine (SAH) in which SAH was found to adopt an alternative conformation and fails to make several key interactions.
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