4o9d | pdb_00004o9d
Structure of Dos1 propeller
Structural highlights
FunctionRAF1_SCHPO Component of the rik1-associated E3 ubiquitin ligase complex that shows ubiquitin ligase activity and is required for histone H3K9 methylation. H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting swi6/HP1 to methylated histones which leads to transcriptional silencing within centromeric heterochromatin, telomeric regions and at the silent mating-type loci. Has a role in both mitotic and meiotic chromosome segregation.[1] [2] [3] Publication Abstract from PubMedRepressive histone H3 lysine 9 methylation (H3K9me) and its recognition by HP1 proteins are necessary for pericentromeric heterochromatin formation. In Schizosaccharomyces pombe, H3K9me deposition depends on the RNAi pathway. Cryptic loci regulator 4 (Clr4), the only known H3K9 methyltransferase in this organism, is a subunit of the Clr4 methyltransferase complex (CLRC), whose composition is reminiscent of a CRL4 type cullin-RING ubiquitin ligase (CRL) including its cullin Cul4, the RING-box protein Pip1, the DNA damage binding protein 1 homolog Rik1, and the DCAF-like protein delocalization of Swi6 1 (Dos1). Dos2 and Stc1 have been proposed to be part of the complex but do not bear similarity to canonical ubiquitin ligase components. CLRC is an active E3 ligase in vitro, and this activity is necessary for heterochromatin assembly in vivo. The similarity between CLRC and the CRLs suggests that the WD repeat protein Dos1 will act to mediate target recognition and substrate specificity for CLRC. Here, we present a pairwise interaction screen that confirms a CRL4-like subunit arrangement and further identifies Dos2 as a central component of the complex and recruiter of Stc1. We determined the crystal structure of the Dos1 WD repeat domain, revealing an eight-bladed beta-propeller fold. Functional mapping of the putative target-binding surface of Dos1 identifies key residues required for heterochromatic silencing, consistent with Dos1's role as the specificity factor for the E3 ubiquitin ligase. CRL4-like Clr4 complex in Schizosaccharomyces pombe depends on an exposed surface of Dos1 for heterochromatin silencing.,Kuscu C, Zaratiegui M, Kim HS, Wah DA, Martienssen RA, Schalch T, Joshua-Tor L Proc Natl Acad Sci U S A. 2014 Feb 4;111(5):1795-800. doi:, 10.1073/pnas.1313096111. Epub 2014 Jan 21. PMID:24449894[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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