| Structural highlights
5fg0 is a 2 chain structure with sequence from Baker's yeast. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , |
| Related: | 5fg1 |
| Gene: | RKR1, LTN1, YMR247C, YM9408.09C, YM9920.01C (Baker's yeast) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[LTN1_YEAST] E3 ubiquitin-protein ligase component of the ribosome quality control complex (RQC), a ribosome-associated complex that mediates ubiquitination and extraction of incompletely synthesized nascent chains for proteasomal degradation (PubMed:23178123). Mediates ubiquitination of proteins derived from mRNAs lacking stop codons (non-stop proteins) and other translation arrest products induced by poly-lysine sequences and tandem rare codons. Ubiquitination leads to CDC48 recruitment for extraction and degradation of the incomplete translation product (PubMed:20835226, PubMed:23825054, PubMed:24261871). May indirectly play a role in chromatin function and transcription (PubMed:17283062).[1] [2] [3] [4] [5]
Publication Abstract from PubMed
The Ltn1 E3 ligase (listerin in mammals) has emerged as a paradigm for understanding ribosome-associated ubiquitylation. Ltn1 binds to 60S ribosomal subunits to ubiquitylate nascent polypeptides that become stalled during synthesis; among Ltn1's substrates are aberrant products of mRNA lacking stop codons [nonstop translation products (NSPs)]. Here, we report the reconstitution of NSP ubiquitylation in Neurospora crassa cell extracts. Upon translation in vitro, ribosome-stalled NSPs were ubiquitylated in an Ltn1-dependent manner, while still ribosome-associated. Furthermore, we provide biochemical evidence that the conserved N-terminal domain (NTD) plays a significant role in the binding of Ltn1 to 60S ribosomal subunits and that NTD mutations causing defective 60S binding also lead to defective NSP ubiquitylation, without affecting Ltn1's intrinsic E3 ligase activity. Finally, we report the crystal structure of the Ltn1 NTD at 2.4-A resolution. The structure, combined with additional mutational studies, provides insight to NTD's role in binding stalled 60S subunits. Our findings show that Neurospora extracts can be used as a tool to dissect mechanisms underlying ribosome-associated protein quality control and are consistent with a model in which Ltn1 uses 60S subunits as adapters, at least in part via its NTD, to target stalled NSPs for ubiquitylation.
Structure and function of the yeast listerin (Ltn1) conserved N-terminal domain in binding to stalled 60S ribosomal subunits.,Doamekpor SK, Lee JW, Hepowit NL, Wu C, Charenton C, Leonard M, Bengtson MH, Rajashankar KR, Sachs MS, Lima CD, Joazeiro CA Proc Natl Acad Sci U S A. 2016 Jul 19;113(29):E4151-60. doi:, 10.1073/pnas.1605951113. Epub 2016 Jul 6. PMID:27385828[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Braun MA, Costa PJ, Crisucci EM, Arndt KM. Identification of Rkr1, a nuclear RING domain protein with functional connections to chromatin modification in Saccharomyces cerevisiae. Mol Cell Biol. 2007 Apr;27(8):2800-11. Epub 2007 Feb 5. PMID:17283062 doi:http://dx.doi.org/10.1128/MCB.01947-06
- ↑ Bengtson MH, Joazeiro CA. Role of a ribosome-associated E3 ubiquitin ligase in protein quality control. Nature. 2010 Sep 23;467(7314):470-3. doi: 10.1038/nature09371. Epub 2010 Sep 12. PMID:20835226 doi:http://dx.doi.org/10.1038/nature09371
- ↑ Brandman O, Stewart-Ornstein J, Wong D, Larson A, Williams CC, Li GW, Zhou S, King D, Shen PS, Weibezahn J, Dunn JG, Rouskin S, Inada T, Frost A, Weissman JS. A ribosome-bound quality control complex triggers degradation of nascent peptides and signals translation stress. Cell. 2012 Nov 21;151(5):1042-54. doi: 10.1016/j.cell.2012.10.044. PMID:23178123 doi:http://dx.doi.org/10.1016/j.cell.2012.10.044
- ↑ Letzring DP, Wolf AS, Brule CE, Grayhack EJ. Translation of CGA codon repeats in yeast involves quality control components and ribosomal protein L1. RNA. 2013 Sep;19(9):1208-17. doi: 10.1261/rna.039446.113. Epub 2013 Jul 3. PMID:23825054 doi:http://dx.doi.org/10.1261/rna.039446.113
- ↑ Matsuda R, Ikeuchi K, Nomura S, Inada T. Protein quality control systems associated with no-go and nonstop mRNA surveillance in yeast. Genes Cells. 2014 Jan;19(1):1-12. doi: 10.1111/gtc.12106. Epub 2013 Nov 21. PMID:24261871 doi:http://dx.doi.org/10.1111/gtc.12106
- ↑ Doamekpor SK, Lee JW, Hepowit NL, Wu C, Charenton C, Leonard M, Bengtson MH, Rajashankar KR, Sachs MS, Lima CD, Joazeiro CA. Structure and function of the yeast listerin (Ltn1) conserved N-terminal domain in binding to stalled 60S ribosomal subunits. Proc Natl Acad Sci U S A. 2016 Jul 19;113(29):E4151-60. doi:, 10.1073/pnas.1605951113. Epub 2016 Jul 6. PMID:27385828 doi:http://dx.doi.org/10.1073/pnas.1605951113
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