Thiamine pyrophosphate-specific riboswitch
Escherichia coli (bacteria)
The final decision about “that protein is really needed in cells now at this moment?” is done after matured mRNAs are made. If the protein was really needed at that time, translation would start immediately. On the other hand, if it was better to postpone protein production, a mechanism which interrupts the translation would work. There are different mechanisms in prokaryotes and eukaryotes that execute translation timing control.
In eukaryotes, matured mRNAs have 5' cap edited region indicating where translation should start. When the translation should be paused, repressor proteins will bind to 5' cap or interrupt the connection between 5' cap and 3' polyA tail, that is the check point of eukaryotic pre-translational quality control.
On the other hand, prokaryotic bacteria have a conserved stretch of six nucleotides, termed Shine-Dalgarno sequence, that is located at a few nucleotides upstream of the AUG at which translation is to begin. The first step of translation is binding of part of small ribosomal subunit to the Shine-Dalgarno sequence, and subsequently the rest of the ribosomal machinery is loaded onto the given mRNA. Pausing mechanism relies on protein-RNA interactions, where translational repressor proteins bind to the Shine-Dalgarno sequence, and block the access to ribosomal proteins. Not only proteins but also metabolites, which are present in excess in cells, may bind tightly to the Shine-Dalgarno sequence, occupying the small ribosomal subunit and interrupting the translation.
The structure shown here is the complex between bacterial mRNA and metabolite. This part of mRNAs is called riboswitch and located at non-coding region of mRNA. It is sensing the amount of metabolites in a cell, and controlling the translation of proteins that are related to the metabolite. In the present case, the metabolite is the active form of vitamin B1, thiamine pyrophosphate (TPP), composed of three parts: 4-amino-5-hydroxylmethyl-2-methyl pyrimidine moiety (HMP), thiazole moiety, and pyrophosphate moiety. In this complex structure, both edges of TPP (HMP and pyrophosphate moiety) are gripped by two main helices of mRNA, and positioned perpendicular against two helices. Middle part of TPP is not recognized directly. This structure indicates that this riboswitch works as a nano-scale measuring device by checking the distance between both edges of TPP.
Protein Data Bank (PDB)
author: Sachiyo Nomura