National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)
ZIA-DK075136
米国
引用
ジャーナル: Nat Struct Mol Biol / 年: 2019 タイトル: Structural basis of amino acid surveillance by higher-order tRNA-mRNA interactions. 著者: Shuang Li / Zhaoming Su / Jean Lehmann / Vassiliki Stamatopoulou / Nikoleta Giarimoglou / Frances E Henderson / Lixin Fan / Grigore D Pintilie / Kaiming Zhang / Muyuan Chen / Steven J Ludtke ...著者: Shuang Li / Zhaoming Su / Jean Lehmann / Vassiliki Stamatopoulou / Nikoleta Giarimoglou / Frances E Henderson / Lixin Fan / Grigore D Pintilie / Kaiming Zhang / Muyuan Chen / Steven J Ludtke / Yun-Xing Wang / Constantinos Stathopoulos / Wah Chiu / Jinwei Zhang / 要旨: Amino acid availability in Gram-positive bacteria is monitored by T-box riboswitches. T-boxes directly bind tRNAs, assess their aminoacylation state, and regulate the transcription or translation of ...Amino acid availability in Gram-positive bacteria is monitored by T-box riboswitches. T-boxes directly bind tRNAs, assess their aminoacylation state, and regulate the transcription or translation of downstream genes to maintain nutritional homeostasis. Here, we report cocrystal and cryo-EM structures of Geobacillus kaustophilus and Bacillus subtilis T-box-tRNA complexes, detailing their multivalent, exquisitely selective interactions. The T-box forms a U-shaped molecular vise that clamps the tRNA, captures its 3' end using an elaborate 'discriminator' structure, and interrogates its aminoacylation state using a steric filter fashioned from a wobble base pair. In the absence of aminoacylation, T-boxes clutch tRNAs and form a continuously stacked central spine, permitting transcriptional readthrough or translation initiation. A modeled aminoacyl disrupts tRNA-T-box stacking, severing the central spine and blocking gene expression. Our data establish a universal mechanism of amino acid sensing on tRNAs and gene regulation by T-box riboswitches and exemplify how higher-order RNA-RNA interactions achieve multivalency and specificity.