Hexagonal crystal structure of Tas3 C-terminal alpha motifHexagonal crystal structure of Tas3 C-terminal alpha motif

Structural highlights

3d1d is a 6 chain structure with sequence from Schizosaccharomyces pombe. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.6Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TAS3_SCHPO Has a role in the RNA interference (RNAi) pathway which is important for heterochromatin formation and accurate chromosome segregation. A member of the RNA-induced transcriptional silencing (RITS) complex which is involved in the biosynthesis of dsRNA from primer siRNAs provided by the RNA-directed RNA polymerase (RDRC) complex.[1] [2]

Publication Abstract from PubMed

RNA interference (RNAi) plays a pivotal role in the formation of heterochromatin at the fission yeast centromeres. The RNA-induced transcriptional silencing (RITS) complex, composed of heterochromatic small interfering RNAs (siRNAs), the siRNA-binding protein Ago1, the chromodomain protein Chp1, and the Ago1/Chp1-interacting protein Tas3, provides a physical tether between the RNAi and heterochromatin assembly pathways. Here, we report the structural and functional characterization of a C-terminal Tas3 alpha-helical motif (TAM), which self-associates into a helical polymer and is required for cis spreading of RITS in centromeric DNA regions. Site-directed mutations of key residues within the hydrophobic monomer-monomer interface disrupt Tas3-TAM polymeric self-association in vitro and result in loss of gene silencing, spreading of RITS, and a dramatic reduction in centromeric siRNAs in vivo. These results demonstrate that, in addition to the chromodomain of Chp1 and siRNA-loaded Ago1, Tas3 self-association is required for RITS spreading and efficient heterochromatic gene silencing at centromeric repeat regions.

An alpha motif at Tas3 C terminus mediates RITS cis spreading and promotes heterochromatic gene silencing.,Li H, Motamedi MR, Yip CK, Wang Z, Walz T, Patel DJ, Moazed D Mol Cell. 2009 Apr 24;34(2):155-67. PMID:19394293[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. Motamedi MR, Verdel A, Colmenares SU, Gerber SA, Gygi SP, Moazed D. Two RNAi complexes, RITS and RDRC, physically interact and localize to noncoding centromeric RNAs. Cell. 2004 Dec 17;119(6):789-802. PMID:15607976 doi:10.1016/j.cell.2004.11.034
  2. Verdel A, Jia S, Gerber S, Sugiyama T, Gygi S, Grewal SI, Moazed D. RNAi-mediated targeting of heterochromatin by the RITS complex. Science. 2004 Jan 30;303(5658):672-6. Epub 2004 Jan 2. PMID:14704433 doi:10.1126/science.1093686
  3. Li H, Motamedi MR, Yip CK, Wang Z, Walz T, Patel DJ, Moazed D. An alpha motif at Tas3 C terminus mediates RITS cis spreading and promotes heterochromatic gene silencing. Mol Cell. 2009 Apr 24;34(2):155-67. PMID:19394293 doi:10.1016/j.molcel.2009.02.032

3d1d, resolution 2.60Å

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