7uy5
From Proteopedia
(Difference between revisions)
| (One intermediate revision not shown.) | |||
| Line 4: | Line 4: | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7uy5]] is a 10 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=7UY5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UY5 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7uy5]] is a 10 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=7UY5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UY5 FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.5Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=7uy5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7uy5 OCA], [https://pdbe.org/7uy5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7uy5 RCSB], [https://www.ebi.ac.uk/pdbsum/7uy5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7uy5 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=7uy5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7uy5 OCA], [https://pdbe.org/7uy5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7uy5 RCSB], [https://www.ebi.ac.uk/pdbsum/7uy5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7uy5 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| - | + | [https://www.uniprot.org/uniprot/LARP7_TETTS LARP7_TETTS] RNA-binding protein required for assembly of the holoenzyme telomerase ribonucleoprotein (RNP) complex (PubMed:15131081, PubMed:15696174, PubMed:16507983, PubMed:17322903, PubMed:20713447, PubMed:22315458, PubMed:22705372). Telomerase is 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:15696174, PubMed:17322903, PubMed:20713447). TAP65/p65 specifically binds telomerase RNA template TER and is required for biogenesis and placement of the TER stem-terminus element: TAP65/p65 first protects the 3'-end of TER from degradation and acts as a chaperone to correctly fold TER for protein binding; it then bends TER stem-loop IV to position it for interaction of stem-loop IV with catalytic TERT RNA-binding domain (PubMed:15696174, PubMed:17322903, PubMed:20713447, PubMed:22315458, PubMed:22705372).<ref>PMID:15131081</ref> <ref>PMID:15696174</ref> <ref>PMID:16507983</ref> <ref>PMID:17322903</ref> <ref>PMID:20713447</ref> <ref>PMID:22315458</ref> <ref>PMID:22705372</ref> | |
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
Telomeres are the physical ends of linear chromosomes. They are composed of short repeating sequences (such as TTGGGG in the G-strand for Tetrahymena thermophila) of double-stranded DNA with a single-strand 3' overhang of the G-strand and, in humans, the six shelterin proteins: TPP1, POT1, TRF1, TRF2, RAP1 and TIN2(1,2). TPP1 and POT1 associate with the 3' overhang, with POT1 binding the G-strand(3) and TPP1 (in complex with TIN2(4)) recruiting telomerase via interaction with telomerase reverse transcriptase(5) (TERT). The telomere DNA ends are replicated and maintained by telomerase(6), for the G-strand, and subsequently DNA polymerase alpha-primase(7,8) (PolalphaPrim), for the C-strand(9). PolalphaPrim activity is stimulated by the heterotrimeric complex CTC1-STN1-TEN1(10-12) (CST), but the structural basis of the recruitment of PolalphaPrim and CST to telomere ends remains unknown. Here we report cryo-electron microscopy (cryo-EM) structures of Tetrahymena CST in the context of the telomerase holoenzyme, in both the absence and the presence of PolalphaPrim, and of PolalphaPrim alone. Tetrahymena Ctc1 binds telomerase subunit p50, a TPP1 orthologue, on a flexible Ctc1 binding motif revealed by cryo-EM and NMR spectroscopy. The PolalphaPrim polymerase subunit POLA1 binds Ctc1 and Stn1, and its interface with Ctc1 forms an entry port for G-strand DNA to the POLA1 active site. We thus provide a snapshot of four key components that are required for telomeric DNA synthesis in a single active complex-telomerase-core ribonucleoprotein, p50, CST and PolalphaPrim-that provides insights into the recruitment of CST and PolalphaPrim and the handoff between G-strand and C-strand synthesis. | Telomeres are the physical ends of linear chromosomes. They are composed of short repeating sequences (such as TTGGGG in the G-strand for Tetrahymena thermophila) of double-stranded DNA with a single-strand 3' overhang of the G-strand and, in humans, the six shelterin proteins: TPP1, POT1, TRF1, TRF2, RAP1 and TIN2(1,2). TPP1 and POT1 associate with the 3' overhang, with POT1 binding the G-strand(3) and TPP1 (in complex with TIN2(4)) recruiting telomerase via interaction with telomerase reverse transcriptase(5) (TERT). The telomere DNA ends are replicated and maintained by telomerase(6), for the G-strand, and subsequently DNA polymerase alpha-primase(7,8) (PolalphaPrim), for the C-strand(9). PolalphaPrim activity is stimulated by the heterotrimeric complex CTC1-STN1-TEN1(10-12) (CST), but the structural basis of the recruitment of PolalphaPrim and CST to telomere ends remains unknown. Here we report cryo-electron microscopy (cryo-EM) structures of Tetrahymena CST in the context of the telomerase holoenzyme, in both the absence and the presence of PolalphaPrim, and of PolalphaPrim alone. Tetrahymena Ctc1 binds telomerase subunit p50, a TPP1 orthologue, on a flexible Ctc1 binding motif revealed by cryo-EM and NMR spectroscopy. The PolalphaPrim polymerase subunit POLA1 binds Ctc1 and Stn1, and its interface with Ctc1 forms an entry port for G-strand DNA to the POLA1 active site. We thus provide a snapshot of four key components that are required for telomeric DNA synthesis in a single active complex-telomerase-core ribonucleoprotein, p50, CST and PolalphaPrim-that provides insights into the recruitment of CST and PolalphaPrim and the handoff between G-strand and C-strand synthesis. | ||
| - | Structure of Tetrahymena telomerase-bound CST with polymerase alpha-primase.,He Y, Song H, Chan H, Liu B, Wang Y, Susac L, Zhou ZH, Feigon J Nature. 2022 Aug;608(7924):813-818. doi: 10.1038/s41586-022-04931-7. Epub 2022, Jul 13. PMID:35831498<ref>PMID:35831498</ref> | + | Structure of Tetrahymena telomerase-bound CST with polymerase alpha-primase.,He Y, Song H, Chan H, Liu B, Wang Y, Susac L, Zhou ZH, Feigon J Nature. 2022 Aug;608(7924):813-818. doi: 10.1038/s41586-022-04931-7. Epub 2022 , Jul 13. PMID:35831498<ref>PMID:35831498</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 7uy5" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 7uy5" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Telomerase 3D structures|Telomerase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
Tetrahymena telomerase with CST
| |||||||||||
Categories: Large Structures | Tetrahymena thermophila | Chan H | Feigon J | He Y | Liu B | Song H | Susac L | Wang Y | Zhou ZH
