6QSZ

Crystal structure of the Sir4 H-BRCT domain in complex with Esc1 pS1450 peptide

Summary for 6QSZ

• Entry DOI: 10.2210/pdb6qsz/pdb
• Descriptor: Regulatory protein SIR4, Silent chromatin protein ESC1, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: heterochromatin, nuclear protein
• Biological source: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast); More
• Total number of polymer chains: 16
• Total formula weight: 134973.60

Authors

Deshpande, I.,Keusch, J.J.,Challa, K.,Iesmantavicius, V.,Gasser, S.M.,Gut, H. (deposition date: 2019-02-22, release date: 2019-09-18, Last modification date: 2024-10-23)

Primary citation

Deshpande, I.,Keusch, J.J.,Challa, K.,Iesmantavicius, V.,Gasser, S.M.,Gut, H.
The Sir4 H-BRCT domain interacts with phospho-proteins to sequester and repress yeast heterochromatin.
Embo J., 38:e101744-e101744, 2019

PubMed Abstract: 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.

PubMed: 31515872
DOI: 10.15252/embj.2019101744

Experimental method

X-RAY DIFFRACTION (2.5 Å)