5c9h

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Structural Basis of Template Boundary Definition in Tetrahymena TelomeraseStructural Basis of Template Boundary Definition in Tetrahymena Telomerase

Structural highlights

5c9h is a 6 chain structure with sequence from Tetrahymena thermophila. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TERT_TETTS Catalytic component of telomerase, an essential ribonucleoprotein enzyme that copies new telomeric repeats onto chromosome ends by repetitively synthesizing the short telomere-repeat sequence 5'-TTGGGG-3' using an RNA template component TER (PubMed:10944124, PubMed:15696174, PubMed:17322903, PubMed:20713447, PubMed:16462747). TERT is a reverse transcriptase that adds simple sequence repeats to chromosome ends by copying a template sequence within the RNA component of the enzyme (PubMed:10944124, PubMed:15696174, PubMed:17322903, PubMed:20713447, PubMed:16462747).[1] [2] [3] [4] [5]

Publication Abstract from PubMed

Telomerase is required to maintain repetitive G-rich telomeric DNA sequences at chromosome ends. To do so, the telomerase reverse transcriptase (TERT) subunit reiteratively uses a small region of the integral telomerase RNA (TER) as a template. An essential feature of telomerase catalysis is the strict definition of the template boundary to determine the precise TER nucleotides to be reverse transcribed by TERT. We report the 3-A crystal structure of the Tetrahymena TERT RNA-binding domain (tTRBD) bound to the template boundary element (TBE) of TER. tTRBD is wedged into the base of the TBE RNA stem-loop, and each of the flanking RNA strands wraps around opposite sides of the protein domain. The structure illustrates how the tTRBD establishes the template boundary by positioning the TBE at the correct distance from the TERT active site to prohibit copying of nontemplate nucleotides.

Structural basis of template-boundary definition in Tetrahymena telomerase.,Jansson LI, Akiyama BM, Ooms A, Lu C, Rubin SM, Stone MD Nat Struct Mol Biol. 2015 Oct 5. doi: 10.1038/nsmb.3101. PMID:26436828[6]

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

See Also

References

  1. Miller MC, Liu JK, Collins K. Template definition by Tetrahymena telomerase reverse transcriptase. EMBO J. 2000 Aug 15;19(16):4412-22. PMID:10944124 doi:10.1093/emboj/19.16.4412
  2. Prathapam R, Witkin KL, O'Connor CM, Collins K. A telomerase holoenzyme protein enhances telomerase RNA assembly with telomerase reverse transcriptase. Nat Struct Mol Biol. 2005 Mar;12(3):252-7. doi: 10.1038/nsmb900. Epub 2005 Feb 6. PMID:15696174 doi:http://dx.doi.org/10.1038/nsmb900
  3. Jacobs SA, Podell ER, Cech TR. Crystal structure of the essential N-terminal domain of telomerase reverse transcriptase. Nat Struct Mol Biol. 2006 Mar;13(3):218-25. Epub 2006 Feb 5. PMID:16462747 doi:10.1038/nsmb1054
  4. Stone MD, Mihalusova M, O'connor CM, Prathapam R, Collins K, Zhuang X. Stepwise protein-mediated RNA folding directs assembly of telomerase ribonucleoprotein. Nature. 2007 Mar 22;446(7134):458-61. doi: 10.1038/nature05600. Epub 2007 Feb 25. PMID:17322903 doi:http://dx.doi.org/10.1038/nature05600
  5. Berman AJ, Gooding AR, Cech TR. Tetrahymena telomerase protein p65 induces conformational changes throughout telomerase RNA (TER) and rescues telomerase reverse transcriptase and TER assembly mutants. Mol Cell Biol. 2010 Oct;30(20):4965-76. doi: 10.1128/MCB.00827-10. Epub 2010 Aug , 16. PMID:20713447 doi:http://dx.doi.org/10.1128/MCB.00827-10
  6. Jansson LI, Akiyama BM, Ooms A, Lu C, Rubin SM, Stone MD. Structural basis of template-boundary definition in Tetrahymena telomerase. Nat Struct Mol Biol. 2015 Oct 5. doi: 10.1038/nsmb.3101. PMID:26436828 doi:http://dx.doi.org/10.1038/nsmb.3101

5c9h, resolution 3.00Å

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OCA