5we0

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Structural Basis for Shelterin Bridge AssemblyStructural Basis for Shelterin Bridge Assembly

Structural highlights

5we0 is a 12 chain structure with sequence from Fission yeast. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:poz1, SPAC19G12.13c (Fission yeast), tpz1, mug169, SPAC6F6.16c, SPAC6F6.18c (Fission yeast), rap1, SPBC1778.02 (Fission yeast)
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[POZ1_SCHPO] Telomeric DNA-binding protein that negatively regulates telomerase and telomere length.[1] [RAP1_SCHPO] Involved in the regulation of telomere length, clustering and has a specific role in telomere position effect (TPE). Unlike yeast, exhibits no effect in transcription regulation.[2] [3] [4] [TPZ1_SCHPO] Telomeric DNA-binding protein that is required to protect the 3'-end telomeric overhang and involved in telomere length regulation. recruits poz1 and ccq1 to telomeres, regulating telomere length negatively and positivels respectively.[5] [6]

Publication Abstract from PubMed

Telomere elongation through telomerase enables chromosome survival during cellular proliferation. The conserved multifunctional shelterin complex associates with telomeres to coordinate multiple telomere activities, including telomere elongation by telomerase. Similar to the human shelterin, fission yeast shelterin is composed of telomeric sequence-specific double- and single-stranded DNA-binding proteins, Taz1 and Pot1, respectively, bridged by Rap1, Poz1, and Tpz1. Here, we report the crystal structure of the fission yeast Tpz1(475-508)-Poz1-Rap1(467-496) complex that provides the structural basis for shelterin bridge assembly. Biochemical analyses reveal that shelterin bridge assembly is a hierarchical process in which Tpz1 binding to Poz1 elicits structural changes in Poz1, allosterically promoting Rap1 binding to Poz1. Perturbation of the cooperative Tpz1-Poz1-Rap1 assembly through mutation of the "conformational trigger" in Poz1 leads to unregulated telomere lengthening. Furthermore, we find that the human shelterin counterparts TPP1-TIN2-TRF2 also assemble hierarchically, indicating cooperativity as a conserved driving force for shelterin assembly.

Structural Basis for Shelterin Bridge Assembly.,Kim JK, Liu J, Hu X, Yu C, Roskamp K, Sankaran B, Huang L, Komives EA, Qiao F Mol Cell. 2017 Nov 16;68(4):698-714.e5. doi: 10.1016/j.molcel.2017.10.032. PMID:29149597[7]

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

References

  1. ↑ Miyoshi T, Kanoh J, Saito M, Ishikawa F. Fission yeast Pot1-Tpp1 protects telomeres and regulates telomere length. Science. 2008 Jun 6;320(5881):1341-4. doi: 10.1126/science.1154819. PMID:18535244 doi:http://dx.doi.org/10.1126/science.1154819
  2. ↑ Chikashige Y, Hiraoka Y. Telomere binding of the Rap1 protein is required for meiosis in fission yeast. Curr Biol. 2001 Oct 16;11(20):1618-23. PMID:11676924
  3. ↑ Kanoh J, Ishikawa F. spRap1 and spRif1, recruited to telomeres by Taz1, are essential for telomere function in fission yeast. Curr Biol. 2001 Oct 16;11(20):1624-30. PMID:11676925
  4. ↑ Chikashige Y, Yamane M, Okamasa K, Tsutsumi C, Kojidani T, Sato M, Haraguchi T, Hiraoka Y. Membrane proteins Bqt3 and -4 anchor telomeres to the nuclear envelope to ensure chromosomal bouquet formation. J Cell Biol. 2009 Nov 2;187(3):413-27. doi: 10.1083/jcb.200902122. PMID:19948484 doi:http://dx.doi.org/10.1083/jcb.200902122
  5. ↑ Martin-Castellanos C, Blanco M, Rozalen AE, Perez-Hidalgo L, Garcia AI, Conde F, Mata J, Ellermeier C, Davis L, San-Segundo P, Smith GR, Moreno S. A large-scale screen in S. pombe identifies seven novel genes required for critical meiotic events. Curr Biol. 2005 Nov 22;15(22):2056-62. PMID:16303567 doi:http://dx.doi.org/S0960-9822(05)01277-7
  6. ↑ Miyoshi T, Kanoh J, Saito M, Ishikawa F. Fission yeast Pot1-Tpp1 protects telomeres and regulates telomere length. Science. 2008 Jun 6;320(5881):1341-4. doi: 10.1126/science.1154819. PMID:18535244 doi:http://dx.doi.org/10.1126/science.1154819
  7. ↑ Kim JK, Liu J, Hu X, Yu C, Roskamp K, Sankaran B, Huang L, Komives EA, Qiao F. Structural Basis for Shelterin Bridge Assembly. Mol Cell. 2017 Nov 16;68(4):698-714.e5. doi: 10.1016/j.molcel.2017.10.032. PMID:29149597 doi:http://dx.doi.org/10.1016/j.molcel.2017.10.032

5we0, resolution 2.30Å

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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA, Joel L. Sussman
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