RNA recognition and base flipping by the toxin sarcin

• Published in: Journal of synchrotron radiation 2004-01, Vol.11 (1), p.93-96
• Main Authors: Correll, C. C., Yang, X., Gerczei, T., Beneken, J., Plantinga, M. J.
• Format: Article
• Language: English
• Subjects: Binding Sites; Endoribonucleases - chemistry; Endoribonucleases - metabolism; Exact sciences and technology; Fungal Proteins; induced fit; Instruments, apparatus, components and techniques common to several branches of physics and astronomy; Macromolecular Substances; Models, Molecular; Mycotoxins - chemistry; Mycotoxins - metabolism; Nucleotides - chemistry; Nucleotides - metabolism; Physics; Protein Binding; Protein Conformation; Protein Synthesis Inhibitors - chemistry; Protein Synthesis Inhibitors - metabolism; Ribosomes - chemistry; Ribosomes - metabolism; Ricin - chemistry; Ricin - metabolism; RNA motifs; RNA-protein recognition; Structure-Activity Relationship; Synchrotron radiation instrumentation; X- and γ-ray instruments and techniques
• ISSN: 1600-5775; 0909-0495; 1600-5775
• DOI: 10.1107/S0909049503023896

Sarcin is a member of a fungal toxin family that enters cells and specifically cleaves one of the thousands of RNA phosphodiester bonds in the ribosome. As a result, elongation factor binding is disrupted, translation is inhibited and apoptosis is triggered. The toxin targets a universal RNA structure in the ribosome called the sarcin/ricin loop (SRL). A 1.11 Å resolution structure of a minimal SRL RNA substrate (∼30‐mer) shows that the loop portion of the substrate folds into two common building blocks of RNA structure: a bulged‐G motif (recognition site) and a GAGA tetraloop (cleavage site). To elucidate the structural basis of toxin action, two co‐crystal structures of the sarcin homologue restrictocin have beeen determined bound to different analogs of a minimal SRL RNA substrate. Our studies argue that site selection by the toxin depends on direct base and shape recognition of the SRL RNA, and that cleavage by the toxin depends on a base flipping mechanism that positions the nucleophile for in‐line attack on the scissile bond.