Structure of the Dom34-Hbs1 complex and implications for no-go decay.
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 Schizosaccharomyces pombe Dom34-Hbs1 complex reveals an overall shape similar to that of eRF1-eRF3-GTP and EF-Tu-tRNA-GDPNP. Similarly 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.
Chen
Liming
L
Laboratory of Macromolecular Structure, Institute of Molecular and Cell Biology, Proteos, Singapore.
Muhlrad
Denise
D
Hauryliuk
Vasili
V
Cheng
Zhihong
Z
Lim
Meng Kiat
MK
Shyp
Viktoriya
V
Parker
Roy
R
Song
Haiwei
H
D002151:Calorimetry; D018360:Crystallography, X-Ray; D004722:Endoribonucleases / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D008958:Models, Molecular; D010444:Peptide Elongation Factor Tu / Q000737:chemistry; D011485:Protein Binding; D014176:Protein Biosynthesis; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D020871:RNA Stability / Q000502:physiology*; D012331:RNA, Fungal / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D012343:RNA, Transfer / Q000737:chemistry; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D012568:Schizosaccharomyces / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000502:physiology
D012331:RNA, Fungal; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; D006160:Guanosine Triphosphate; D012343:RNA, Transfer; D004722:Endoribonucleases; D010444:Peptide Elongation Factor Tu