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| | <StructureSection load='3u4z' size='340' side='right'caption='[[3u4z]], [[Resolution|resolution]] 2.30Å' scene=''> | | <StructureSection load='3u4z' size='340' side='right'caption='[[3u4z]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3u4z]] is a 2 chain structure with sequence from [https://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 [https://proteopedia.org/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"><div style='overflow: auto; max-height: 3em;'>[[3u4v|3u4v]], [[3u50|3u50]]</div></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]] 2.3Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TAP82 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5911 TETTH])</td></tr>
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| | <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'>[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> |
| | </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.
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| - | 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>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div> | + | |
| - | <div class="pdbe-citations 3u4z" style="background-color:#fffaf0;"></div> | + | |
| | | | |
| | ==See Also== | | ==See Also== |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Tetth]] | + | [[Category: Tetrahymena thermophila]] |
| - | [[Category: Huang, J]] | + | [[Category: Huang J]] |
| - | [[Category: Lei, M]] | + | [[Category: Lei M]] |
| - | [[Category: Yang, Y]] | + | [[Category: Yang Y]] |
| - | [[Category: Zeng, Z]] | + | [[Category: Zeng Z]] |
| - | [[Category: Dna binding protein]]
| + | |
| - | [[Category: Processivity factor]]
| + | |
| - | [[Category: Teb1]]
| + | |
| - | [[Category: Telomerase]]
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| - | [[Category: Tetrahymena]]
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| Structural highlights
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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
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