In an earlier paper by Kaji and colleagues from Sweden, the crystal structure of RRF showed that RRF mimics the L-shape and dimension of tRNA. Chemical probing by Kaji and colleagues at the University of California, Santa Cruz showed the approximate ribosomal binding site of RRF. In the current PNAS paper, direct observation of the RRF-ribosome structure revealed the exact ribosomal position of bound RRF. It further showed that part of the ribosome contorts by a significant amount molecularly speaking when RRF binds to it.
More precisely, the position of the key helices of the ribosomal small and large subunits that hold mRNA move inward, suggesting that this movement may be essential for the release of mRNA from the ribosome. In addition, the RRF binding sites are very close to where the two ribosomal subunits are held together, which explains an earlier observation that the disassembly reaction by RRF may be followed by dissociation of the two subunits.
In short, the recycling process goes like this: RRF, along with EF-G, binds to the ribosome. This promotes the release of tRNAs by the movement of RRF, similar to tRNA movement. "This is the first example of a functional mimic of tRNA by a protein," adds Kaji. After the tRNAs leave, RRF, EF-G, and mRNA also detach from the ribosome. The released ribosome is now empty and free to start a new session of translating mRNA into protein. Where RRF binds is near the key ribosomal spot holding mRNA. "Since the main function of RRF is to release mRNA, this makes sense in terms of function," explains Kaji.
Humans have an RRF analogue in the mitochondria, the respiratory organelle within cells. "One may argue that proposed antibiotics against RRF may influence mitochondrial protein synthesis," notes
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
30-Jun-2004