Structure of the Dom34-Hbs1 complex and implications for no-go decay

Liming Chen; Denise Muhlrad; Vasili Hauryliuk; Zhihong Cheng; Meng Kiat Lim; Viktoriya Shyp; Roy Parker; Haiwei Song

doi:10.1038/nsmb.1922

Structure of the Dom34-Hbs1 complex and implications for no-go decay

Liming Chen, Denise Muhlrad, Vasili Hauryliuk, Zhihong Cheng, Meng Kiat Lim, Viktoriya Shyp, Roy Parker, Haiwei Song

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	1233-1240
Journal	Nature Structural and Molecular Biology
Volume	17
Issue number	10
DOIs	https://doi.org/10.1038/nsmb.1922
Publication status	Published - 2010 Oct
Externally published	Yes

Bibliographical note

Funding Information:
We would like to thank the beamline scientists at ID23-1 (European Synchrotron Radiation Facility (ESRF), France) for assistance and access to synchrotron radiation facilities. This work is financially supported by the Biomedical Research Council of A*STAR (Agency for Science, Technology and Research) (H.S.), European Regional Development Fund through the Center of Excellence in Chemical Biology (V.H.) and by the Howard Hughes Medical Institute (R.P.).

Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.

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Biochemistry and Molecular Biology

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10.1038/nsmb.1922

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title = "Structure of the Dom34-Hbs1 complex and implications for no-go decay",

abstract = "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.",

author = "Liming Chen and Denise Muhlrad and Vasili Hauryliuk and Zhihong Cheng and Lim, {Meng Kiat} and Viktoriya Shyp and Roy Parker and Haiwei Song",

note = "Funding Information: We would like to thank the beamline scientists at ID23-1 (European Synchrotron Radiation Facility (ESRF), France) for assistance and access to synchrotron radiation facilities. This work is financially supported by the Biomedical Research Council of A*STAR (Agency for Science, Technology and Research) (H.S.), European Regional Development Fund through the Center of Excellence in Chemical Biology (V.H.) and by the Howard Hughes Medical Institute (R.P.). Copyright: Copyright 2010 Elsevier B.V., All rights reserved.",

year = "2010",

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doi = "10.1038/nsmb.1922",

language = "English",

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pages = "1233--1240",

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AU - Chen, Liming

AU - Muhlrad, Denise

AU - Hauryliuk, Vasili

AU - Cheng, Zhihong

AU - Lim, Meng Kiat

AU - Shyp, Viktoriya

AU - Parker, Roy

AU - Song, Haiwei

N1 - Funding Information: We would like to thank the beamline scientists at ID23-1 (European Synchrotron Radiation Facility (ESRF), France) for assistance and access to synchrotron radiation facilities. This work is financially supported by the Biomedical Research Council of A*STAR (Agency for Science, Technology and Research) (H.S.), European Regional Development Fund through the Center of Excellence in Chemical Biology (V.H.) and by the Howard Hughes Medical Institute (R.P.). Copyright: Copyright 2010 Elsevier B.V., All rights reserved.

PY - 2010/10

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N2 - 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.

AB - 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.

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Structure of the Dom34-Hbs1 complex and implications for no-go decay

Abstract

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