Structural and biochemical analyses of the DEAD-box ATPase Sub2 in association with THO or Yra1
mRNA is cotranscrptionally processed and packaged into messenger ribonucleoprotein particles (mRNPs) in the nucleus. Prior to export through the nuclear pore, mRNPs undergo several obligatory remodeling reactions. In yeast, one of these reactions involves loading of the mRNA-binding protein Yra1 by...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2017-01-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/20070 |
| _version_ | 1811201023206752256 |
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| author | Yi Ren Philip Schmiege Günter Blobel |
| author_facet | Yi Ren Philip Schmiege Günter Blobel |
| author_sort | Yi Ren |
| collection | DOAJ |
| description | mRNA is cotranscrptionally processed and packaged into messenger ribonucleoprotein particles (mRNPs) in the nucleus. Prior to export through the nuclear pore, mRNPs undergo several obligatory remodeling reactions. In yeast, one of these reactions involves loading of the mRNA-binding protein Yra1 by the DEAD-box ATPase Sub2 as assisted by the hetero-pentameric THO complex. To obtain molecular insights into reaction mechanisms, we determined crystal structures of two relevant complexes: a THO hetero-pentamer bound to Sub2 at 6.0 Å resolution; and Sub2 associated with an ATP analogue, RNA, and a C-terminal fragment of Yra1 (Yra1-C) at 2.6 Å resolution. We found that the 25 nm long THO clamps Sub2 in a half-open configuration; in contrast, when bound to the ATP analogue, RNA and Yra1-C, Sub2 assumes a closed conformation. Both THO and Yra1-C stimulated Sub2’s intrinsic ATPase activity. We propose that THO surveys common landmarks in each nuclear mRNP to localize Sub2 for targeted loading of Yra1. |
| first_indexed | 2024-04-12T02:14:39Z |
| format | Article |
| id | doaj.art-8a0c5e9ac52e4b4189a892024acf2530 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:14:39Z |
| publishDate | 2017-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-8a0c5e9ac52e4b4189a892024acf25302022-12-22T03:52:18ZengeLife Sciences Publications LtdeLife2050-084X2017-01-01610.7554/eLife.20070Structural and biochemical analyses of the DEAD-box ATPase Sub2 in association with THO or Yra1Yi Ren0Philip Schmiege1Günter Blobel2https://orcid.org/0000-0002-7839-8341Laboratory of Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, United StatesLaboratory of Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, United StatesLaboratory of Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, United StatesmRNA is cotranscrptionally processed and packaged into messenger ribonucleoprotein particles (mRNPs) in the nucleus. Prior to export through the nuclear pore, mRNPs undergo several obligatory remodeling reactions. In yeast, one of these reactions involves loading of the mRNA-binding protein Yra1 by the DEAD-box ATPase Sub2 as assisted by the hetero-pentameric THO complex. To obtain molecular insights into reaction mechanisms, we determined crystal structures of two relevant complexes: a THO hetero-pentamer bound to Sub2 at 6.0 Å resolution; and Sub2 associated with an ATP analogue, RNA, and a C-terminal fragment of Yra1 (Yra1-C) at 2.6 Å resolution. We found that the 25 nm long THO clamps Sub2 in a half-open configuration; in contrast, when bound to the ATP analogue, RNA and Yra1-C, Sub2 assumes a closed conformation. Both THO and Yra1-C stimulated Sub2’s intrinsic ATPase activity. We propose that THO surveys common landmarks in each nuclear mRNP to localize Sub2 for targeted loading of Yra1.https://elifesciences.org/articles/20070mRNP remodelingDEAD-box ATPaseX-ray crystallography |
| spellingShingle | Yi Ren Philip Schmiege Günter Blobel Structural and biochemical analyses of the DEAD-box ATPase Sub2 in association with THO or Yra1 eLife mRNP remodeling DEAD-box ATPase X-ray crystallography |
| title | Structural and biochemical analyses of the DEAD-box ATPase Sub2 in association with THO or Yra1 |
| title_full | Structural and biochemical analyses of the DEAD-box ATPase Sub2 in association with THO or Yra1 |
| title_fullStr | Structural and biochemical analyses of the DEAD-box ATPase Sub2 in association with THO or Yra1 |
| title_full_unstemmed | Structural and biochemical analyses of the DEAD-box ATPase Sub2 in association with THO or Yra1 |
| title_short | Structural and biochemical analyses of the DEAD-box ATPase Sub2 in association with THO or Yra1 |
| title_sort | structural and biochemical analyses of the dead box atpase sub2 in association with tho or yra1 |
| topic | mRNP remodeling DEAD-box ATPase X-ray crystallography |
| url | https://elifesciences.org/articles/20070 |
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