| Structural highlights
6qsz is a 16 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: | |
| NonStd Res: | , |
| Gene: | SIR4, ASD1, STE9, UTH2, YDR227W, YD9934.12 (Baker's yeast) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[SIR4_YEAST] The proteins SIR1 through SIR4 are required for transcriptional repression of the silent mating type loci, HML and HMR. The proteins SIR2 through SIR4 repress mulitple loci by modulating chromatin structure. Involves the compaction of chromatin fiber into a more condensed form.[1] [ESC1_YEAST] Involved in the clustering of telomeres at the nuclear periphery, forming discrete subcompartments that accumulate a complex of histone-binding silencing factors like SIR4. Required for SIR4-mediated anchoring and partitioning of plasmids.[2] [3] [4]
Publication Abstract from PubMed
In Saccharomyces cerevisiae, the silent information regulator (SIR) proteins Sir2/3/4 form a complex that suppresses transcription in subtelomeric regions and at the homothallic mating-type (HM) loci. Here, we identify a non-canonical BRCA1 C-terminal domain (H-BRCT) in Sir4, which is responsible for tethering telomeres to the nuclear periphery. We show that Sir4 H-BRCT and the closely related Dbf4 H-BRCT serve as selective phospho-epitope recognition domains that bind to a variety of phosphorylated target peptides. We present detailed structural information about the binding mode of established Sir4 interactors (Esc1, Ty5, Ubp10) and identify several novel interactors of Sir4 H-BRCT, including the E3 ubiquitin ligase Tom1. Based on these findings, we propose a phospho-peptide consensus motif for interaction with Sir4 H-BRCT and Dbf4 H-BRCT. Ablation of the Sir4 H-BRCT phospho-peptide interaction disrupts SIR-mediated repression and perinuclear localization. In conclusion, the Sir4 H-BRCT domain serves as a hub for recruitment of phosphorylated target proteins to heterochromatin to properly regulate silencing and nuclear order.
The Sir4 H-BRCT domain interacts with phospho-proteins to sequester and repress yeast heterochromatin.,Deshpande I, Keusch JJ, Challa K, Iesmantavicius V, Gasser SM, Gut H EMBO J. 2019 Oct 15;38(20):e101744. doi: 10.15252/embj.2019101744. Epub 2019 Sep , 12. PMID:31515872[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Bupp JM, Martin AE, Stensrud ES, Jaspersen SL. Telomere anchoring at the nuclear periphery requires the budding yeast Sad1-UNC-84 domain protein Mps3. J Cell Biol. 2007 Dec 3;179(5):845-54. Epub 2007 Nov 26. PMID:18039933 doi:http://dx.doi.org/10.1083/jcb.200706040
- ↑ Andrulis ED, Zappulla DC, Ansari A, Perrod S, Laiosa CV, Gartenberg MR, Sternglanz R. Esc1, a nuclear periphery protein required for Sir4-based plasmid anchoring and partitioning. Mol Cell Biol. 2002 Dec;22(23):8292-301. doi: 10.1128/mcb.22.23.8292-8301.2002. PMID:12417731 doi:http://dx.doi.org/10.1128/mcb.22.23.8292-8301.2002
- ↑ Taddei A, Hediger F, Neumann FR, Bauer C, Gasser SM. Separation of silencing from perinuclear anchoring functions in yeast Ku80, Sir4 and Esc1 proteins. EMBO J. 2004 Mar 24;23(6):1301-12. doi: 10.1038/sj.emboj.7600144. Epub 2004 Mar, 11. PMID:15014445 doi:http://dx.doi.org/10.1038/sj.emboj.7600144
- ↑ Gartenberg MR, Neumann FR, Laroche T, Blaszczyk M, Gasser SM. Sir-mediated repression can occur independently of chromosomal and subnuclear contexts. Cell. 2004 Dec 29;119(7):955-67. doi: 10.1016/j.cell.2004.11.008. PMID:15620354 doi:http://dx.doi.org/10.1016/j.cell.2004.11.008
- ↑ Deshpande I, Keusch JJ, Challa K, Iesmantavicius V, Gasser SM, Gut H. The Sir4 H-BRCT domain interacts with phospho-proteins to sequester and repress yeast heterochromatin. EMBO J. 2019 Oct 15;38(20):e101744. doi: 10.15252/embj.2019101744. Epub 2019 Sep , 12. PMID:31515872 doi:http://dx.doi.org/10.15252/embj.2019101744
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