Liming Chen1, Denise Muhlrad2, Vasili Hauryliuk3, Zhihong Cheng1, Meng Kiat Lim1, Viktoriya Shyp3, Roy Parker2 and Haiwei Song1,4
1 - Laboratory of Macromolecular Structure, Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, 138673, Singapore.
2 - Department of Molecular and Cellular Biology and Howard Hughes Medical Institute, University of Arizona, Tucson, Arizona 85721, USA.
3 - Department of Biomedical Technology, Institute of Technology, University of Tartu, 1 Nooruse St, Tartu, 50411, Estonia.
4 - Department of Biological Sciences, National University of Singapore, 14 Science Drive, 117543, Singapore.
Published in Nat. Struct. & Mol. Biol. (2010), 17, 1233-1240.
No-go decay (NGD) targets mRNAs with stalls in translation elongation for endonucleolytic cleavage in a process involving the Dom34 and Hbs1 proteins. The crystal structure of a Dom34–Hbs1 complex reveals an overall shape similar to that of eRF1–eRF3–GTP and EF-Tu–tRNA–GDPNP. Similar to eRF1 and GTP binding to eRF3, Dom34 and GTP bind to Hbs1 with strong cooperativity, and Dom34 acts as a GTP-dissociation inhibitor (GDI). A marked conformational change in Dom34 occurs upon binding to Hbs1, leading Dom34 to resemble a portion of a tRNA and to position a conserved basic region in a position expected to be near the peptidyl transferase center. These results support the idea that the Dom34–Hbs1 complex functions to terminate translation and thereby commit mRNAs to NGD. Consistent with this role, NGD at runs of arginine codons, which cause a strong block to elongation, is independent of the Dom34–Hbs1 complex.