The nucleotide-binding site of bacterial translation initiation factor 2 (IF2) as a metabolic sensor
The nucleotide-binding site of bacterial translation initiation factor 2 (IF2) as a metabolic sensor
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DOI：
10.1073/pnas.0606384103
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发表时间：
2006-09-19
影响因子：
11.1
通讯作者：
Gualerzi, Claudio O.
中科院分区：
文献类型：
--
作者：
Milon, Pohl;Tischenko, Eugene;Gualerzi, Claudio O.
翻译起始因子2(1172)是一种鸟嘌呤核苷酸结合蛋白，能与鸟苷3‘，5’-(双)二磷酸(PpGpp)结合，后者是细菌中一种参与严格反应的警报素。在最佳条件下生长的细胞中，GTP浓度很高，ppGpp浓度很低。然而，在胁迫条件下，GTP的浓度可能会下降50%，ppGpp的浓度可以达到与GTP相当的水平。在这里，我们证明了IF2与ppGpp结合在与GTP相同的核苷酸结合部位，并具有类似的亲和力。因此，GTP和丙酮ppGpp可以被认为是两种可供选择的生理相关的IF2配体。PpGpp干扰依赖于IF2的起始复合体的形成，严重抑制起始二肽的形成，阻断翻译的起始步骤。我们的数据表明，IF2具有细胞代谢传感器和调节器的特性，在允许蛋白质合成活跃的条件下，它在活跃的GTP结合形式和当营养缺乏将是有害的，如果不伴随这种合成放缓的情况下，在不活跃的ppGpp结合形式之间振荡。
Translational initiation factor 2 (1172) is a guanine nucleotide-binding protein that can bind guanosine 3',5'-(bis) diphosphate (ppGpp), an alarmone involved in stringent response in bacteria. in cells growing under optimal conditions, the GTP concentration is very high, and that of ppGpp very low. However, under stress conditions, the GTP concentration may decline by as much as 50%, and that of ppGpp can attain levels comparable to those of GTP. Here we show that IF2 binds ppGpp at the same nucleoticle-binding site and with similar affinity as GTP. Thus, GTP and the alarmone ppGpp can be considered two alternative physiologically relevant IF2 ligands. ppGpp interferes with IF2-dependent initiation complex formation, severely inhibits initiation dipeptide formation, and blocks the initiation step of translation. Our data suggest that IF2 has the properties of a cellular metabolic sensor and regulator that oscillates between an active GTP-bound form under conditions allowing active protein syntheses and an inactive ppGpp-bound form when shortage of nutrients would be detrimental, if not accompanied by slackening of this synthesis.