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  Structure and function of Vms1 and Arb1 in RQC and mitochondrial proteome homeostasis

Su, T., Izawa, T., Thoms, M., Yamashita, Y., Cheng, J., Berninghausen, O., et al. (2019). Structure and function of Vms1 and Arb1 in RQC and mitochondrial proteome homeostasis. Nature, 570(7762), 538-542. doi:10.1038/s41586-019-1307-z.

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 Creators:
Su, Ting1, Author
Izawa, Toshiaki2, Author           
Thoms, Matthias1, Author
Yamashita, Yui1, Author
Cheng, Jingdong1, Author
Berninghausen, Otto1, Author
Hartl, F. Ulrich3, Author           
Inada, Toshifumi1, Author
Neupert, Walter2, Author           
Beckmann, Roland1, Author
Affiliations:
1external, ou_persistent22              
2Neupert, Walter / Structure and Function of Mitochondria, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565163              
3Hartl, Franz-Ulrich / Cellular Biochemistry, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565152              

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Free keywords: QUALITY-CONTROL; T-COFFEE; RIBOSOME; TRANSLATION; MECHANISM; SYSTEM; RNA; VISUALIZATION; AGGREGATION; DEGRADATIONScience & Technology - Other Topics;
 Abstract: Ribosome-associated quality control (RQC) provides a rescue pathway for eukaryotic cells to process faulty proteins after translational stalling of cytoplasmic ribosomes(1-6). After dissociation of ribosomes, the stalled tRNA-bound peptide remains associated with the 60S subunit and extended by Rqc2 by addition of C-terminal alanyl and threonyl residues (CAT tails)(7-9), whereas Vms1 catalyses cleavage and release of the peptidyl-tRNA before or after addition of CAT tails(10-12). In doing so, Vms1 counteracts CAT-tailing of nuclear-encoded mitochondrial proteins that otherwise drive aggregation and compromise mitochondrial and cellular homeostasis(13). Here we present structural and functional insights into the interaction of Saccharomyces cerevisiae Vms1 with 60S subunits in pre-and post-peptidyl-tRNA cleavage states. Vms1 binds to 60S subunits with its Vms1-like release factor 1 (VLRF1), zinc finger and ankyrin domains. VLRF1 overlaps with the Rqc2 A-tRNA position and interacts with the ribosomal A-site, projecting its catalytic GSQ motif towards the CCA end of the tRNA, its Y285 residue dislodging the tRNA A73 for nucleolytic cleavage. Moreover, in the pre-state, we found the ABCF-type ATPase Arb1 in the ribosomal E-site, which stabilizes the delocalized A73 of the peptidyl-tRNA and stimulates Vms1-dependent tRNA cleavage. Our structural analysis provides mechanistic insights into the interplay of the RQC factors Vms1, Rqc2 and Arb1 and their role in the protection of mitochondria from the aggregation of toxic proteins.

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Language(s): eng - English
 Dates: 2019
 Publication Status: Published in print
 Pages: 16
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000472860000054
DOI: 10.1038/s41586-019-1307-z
 Degree: -

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Title: Nature
  Abbreviation : Nature
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 570 (7762) Sequence Number: - Start / End Page: 538 - 542 Identifier: ISSN: 0028-0836
CoNE: https://pure.mpg.de/cone/journals/resource/954925427238