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==Crystal Structure of the Tetrahymena telomerase processivity factor Teb1 OB-B==
==Crystal Structure of the Tetrahymena telomerase processivity factor Teb1 OB-B==
<StructureSection load='3u4z' size='340' side='right' caption='[[3u4z]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
<StructureSection load='3u4z' size='340' side='right'caption='[[3u4z]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3u4z]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Tetth Tetth]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3U4Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3U4Z FirstGlance]. <br>
<table><tr><td colspan='2'>[[3u4z]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Tetrahymena_thermophila Tetrahymena thermophila]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3U4Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3U4Z FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3u4v|3u4v]], [[3u50|3u50]]</td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TAP82 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5911 TETTH])</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3u4z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u4z OCA], [https://pdbe.org/3u4z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3u4z RCSB], [https://www.ebi.ac.uk/pdbsum/3u4z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3u4z ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3u4z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u4z OCA], [http://pdbe.org/3u4z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3u4z RCSB], [http://www.ebi.ac.uk/pdbsum/3u4z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3u4z ProSAT]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
== Function ==
== Publication Abstract from PubMed ==
[https://www.uniprot.org/uniprot/TEB1_TETTS TEB1_TETTS] Single-stranded DNA (ssDNA)-binding protein that mediates the recruitment of telomerase to telomeric DNA (PubMed:19941821, PubMed:20363756, PubMed:25225329, PubMed:22143754). Telomerase is an essential ribonucleoprotein (RNP) 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:19941821). Acts as part of a replication protein A (RPA)-related subcomplex of the holoenzyme telomerase ribonucleoprotein complex: TEB1 specifically recognizes and binds telomeric ssDNA, thereby mediating the recruitment of the holoenzyme telomerase RNP complex to telomeres (PubMed:19941821, PubMed:25225329, PubMed:27895115). TEB1 is related to RPA1 subunit of the RPA complex but is specific to telomeric DNA, which is not the case of RPA1 (PubMed:25225329).<ref>PMID:19941821</ref> <ref>PMID:20363756</ref> <ref>PMID:22143754</ref> <ref>PMID:25225329</ref> <ref>PMID:27895115</ref>
Telomerase copies its internal RNA template to synthesize telomeric DNA repeats. Unlike other polymerases, telomerase can retain its single-stranded product through multiple rounds of template dissociation and repositioning to accomplish repeat addition processivity (RAP). Tetrahymena telomerase holoenzyme RAP depends on a subunit, Teb1, with autonomous DNA-binding activity. Sequence homology and domain modeling suggest that Teb1 is a paralog of RPA70C, the largest subunit of the single-stranded DNA-binding factor replication protein (RPA), but unlike RPA, Teb1 binds DNA with high specificity for telomeric repeats. To understand the structural basis and significance of telomeric-repeat DNA recognition by Teb1, we solved crystal structures of three proposed Teb1 DNA-binding domains and defined amino acids of each domain that contribute to DNA interaction. Our studies indicate that two central Teb1 DNA-binding oligonucleotide/oligosaccharide-binding-fold domains, Teb1A and Teb1B, achieve high affinity and selectivity of telomeric-repeat recognition by principles similar to the telomere end-capping protein POT1 (protection of telomeres 1). An additional C-terminal Teb1 oligonucleotide/oligosaccharide-binding-fold domain, Teb1C, has features shared with the RPA70 C-terminal domain including a putative direct DNA-binding surface that is critical for high-RAP activity of reconstituted holoenzyme. The Teb1C zinc ribbon motif does not contribute to DNA binding but is nonetheless required for high-RAP activity, perhaps contributing to Teb1 physical association with the remainder of the holoenzyme. Our results suggest the biological model that high-affinity DNA binding by Teb1AB recruits holoenzyme to telomeres and subsequent Teb1C-DNA association traps product in a sliding-clamp-like manner that does not require high-affinity DNA binding for high stability of enzyme-product association.


Structural basis for Tetrahymena telomerase processivity factor Teb1 binding to single-stranded telomeric-repeat DNA.,Zeng Z, Min B, Huang J, Hong K, Yang Y, Collins K, Lei M Proc Natl Acad Sci U S A. 2011 Dec 20;108(51):20357-61. Epub 2011 Dec 5. PMID:22143754<ref>PMID:22143754</ref>
==See Also==
 
*[[Telomerase-associated protein|Telomerase-associated protein]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3u4z" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Tetth]]
[[Category: Large Structures]]
[[Category: Huang, J]]
[[Category: Tetrahymena thermophila]]
[[Category: Lei, M]]
[[Category: Huang J]]
[[Category: Yang, Y]]
[[Category: Lei M]]
[[Category: Zeng, Z]]
[[Category: Yang Y]]
[[Category: Dna binding protein]]
[[Category: Zeng Z]]
[[Category: Processivity factor]]
[[Category: Teb1]]
[[Category: Telomerase]]
[[Category: Tetrahymena]]

Latest revision as of 13:17, 1 March 2024

Crystal Structure of the Tetrahymena telomerase processivity factor Teb1 OB-BCrystal Structure of the Tetrahymena telomerase processivity factor Teb1 OB-B

Structural highlights

3u4z is a 2 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 2.3Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TEB1_TETTS Single-stranded DNA (ssDNA)-binding protein that mediates the recruitment of telomerase to telomeric DNA (PubMed:19941821, PubMed:20363756, PubMed:25225329, PubMed:22143754). Telomerase is an essential ribonucleoprotein (RNP) 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:19941821). Acts as part of a replication protein A (RPA)-related subcomplex of the holoenzyme telomerase ribonucleoprotein complex: TEB1 specifically recognizes and binds telomeric ssDNA, thereby mediating the recruitment of the holoenzyme telomerase RNP complex to telomeres (PubMed:19941821, PubMed:25225329, PubMed:27895115). TEB1 is related to RPA1 subunit of the RPA complex but is specific to telomeric DNA, which is not the case of RPA1 (PubMed:25225329).[1] [2] [3] [4] [5]

See Also

References

  1. ↑ Min B, Collins K. An RPA-related sequence-specific DNA-binding subunit of telomerase holoenzyme is required for elongation processivity and telomere maintenance. Mol Cell. 2009 Nov 25;36(4):609-19. PMID:19941821 doi:10.1016/j.molcel.2009.09.041
  2. ↑ Min B, Collins K. Multiple mechanisms for elongation processivity within the reconstituted tetrahymena telomerase holoenzyme. J Biol Chem. 2010 May 28;285(22):16434-43. PMID:20363756 doi:10.1074/jbc.M110.119172
  3. ↑ Zeng Z, Min B, Huang J, Hong K, Yang Y, Collins K, Lei M. Structural basis for Tetrahymena telomerase processivity factor Teb1 binding to single-stranded telomeric-repeat DNA. Proc Natl Acad Sci U S A. 2011 Dec 20;108(51):20357-61. Epub 2011 Dec 5. PMID:22143754 doi:10.1073/pnas.1113624108
  4. ↑ Upton HE, Hong K, Collins K. Direct single-stranded DNA binding by Teb1 mediates the recruitment of Tetrahymena thermophila telomerase to telomeres. Mol Cell Biol. 2014 Nov 15;34(22):4200-12. PMID:25225329 doi:10.1128/MCB.01030-14
  5. ↑ Upton HE, Chan H, Feigon J, Collins K. Shared Subunits of Tetrahymena Telomerase Holoenzyme and Replication Protein A Have Different Functions in Different Cellular Complexes. J Biol Chem. 2017 Jan 6;292(1):217-228. PMID:27895115 doi:10.1074/jbc.M116.763664

3u4z, resolution 2.30Å

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