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Detection of Toxin Translocation into the Host Cytosol by Surface Plasmon Resonance
Published on: January 3, 2012
RNA recognition and base flipping by the toxin sarcin
C C Correll1, X Yang, T Gerczei
1Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA. ccorrell@uchicago.edu
Journal of Synchrotron Radiation
|December 4, 2003
Summary
This study reveals how fungal toxins, like restrictocin, target and cleave ribosomal RNA. Understanding this mechanism, involving base flipping and RNA structure recognition, is key to inhibiting protein translation and triggering apoptosis.
Area of Science:
- Molecular Biology
- Structural Biology
- Biochemistry
Background:
- Sarcin is a fungal toxin that inhibits protein translation by cleaving ribosomal RNA.
- The toxin targets a conserved RNA structure known as the sarcin/ricin loop (SRL).
- The SRL contains distinct motifs crucial for both toxin recognition and cleavage.
Purpose of the Study:
- To elucidate the structural basis of sarcin toxin action on the SRL.
- To understand the molecular mechanisms of site selection and RNA cleavage.
Main Methods:
- Determined two co-crystal structures of restrictocin (a sarcin homologue) bound to SRL RNA analogs.
- Utilized high-resolution X-ray crystallography (1.11 Å resolution).
Main Results:
- Identified direct base and shape recognition of the SRL by the toxin for site selection.
- Revealed a base-flipping mechanism enabling the toxin to position the nucleophile for RNA cleavage.
- The SRL RNA substrate adopts a structure with a bulged-G motif and a GAGA tetraloop.
Conclusions:
- Toxin-mediated RNA cleavage involves precise recognition of SRL structure.
- A base-flipping mechanism is central to the catalytic activity of sarcin-family toxins.
- These findings provide insights into the inhibition of protein synthesis and induction of apoptosis.
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