8gap

From Proteopedia

(Difference between revisions)

Revision as of 21:19, 28 June 2023

Structure of LARP7 protein p65-telomerase RNA complex in telomerase

Structural highlights

8gap is a 8 chain structure with sequence from Tetrahymena thermophila and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.8Å
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

La-related protein 7 (LARP7) are a family of RNA chaperones that protect the 3'-end of RNA and are components of specific ribonucleoprotein complexes (RNP). In Tetrahymena thermophila telomerase, LARP7 protein p65 together with telomerase reverse transcriptase (TERT) and telomerase RNA (TER) form the core RNP. p65 has four known domains-N-terminal domain (NTD), La motif (LaM), RNA recognition motif 1 (RRM1), and C-terminal xRRM2. To date, only the xRRM2 and LaM and their interactions with TER have been structurally characterized. Conformational dynamics leading to low resolution in cryo-EM density maps have limited our understanding of how full-length p65 specifically recognizes and remodels TER for telomerase assembly. Here, we combined focused classification of Tetrahymena telomerase cryo-EM maps with NMR spectroscopy to determine the structure of p65-TER. Three previously unknown helices are identified, one in the otherwise intrinsically disordered NTD that binds the La module, one that extends RRM1, and another preceding xRRM2, that stabilize p65-TER interactions. The extended La module (alphaN, LaM and RRM1) interacts with the four 3' terminal U nucleotides, while LaM and alphaN additionally interact with TER pseudoknot, and LaM with stem 1 and 5' end. Our results reveal the extensive p65-TER interactions that promote TER 3'-end protection, TER folding, and core RNP assembly and stabilization. The structure of full-length p65 with TER also sheds light on the biological roles of genuine La and LARP7 proteins as RNA chaperones and core RNP components.

Structure of LARP7 Protein p65-telomerase RNA Complex in Telomerase Revealed by Cryo-EM and NMR.,Wang Y, He Y, Wang Y, Yang Y, Singh M, Eichhorn CD, Cheng X, Xiao Jiang Y, Hong Zhou Z, Feigon J J Mol Biol. 2023 Mar 20:168044. doi: 10.1016/j.jmb.2023.168044. PMID:37330293^[6]

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

References

↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ Wang Y, He Y, Wang Y, Yang Y, Singh M, Eichhorn CD, Cheng X, Xiao Jiang Y, Hong Zhou Z, Feigon J. Structure of LARP7 Protein p65-telomerase RNA Complex in Telomerase Revealed by Cryo-EM and NMR. J Mol Biol. 2023 Mar 20:168044. PMID:37330293 doi:10.1016/j.jmb.2023.168044

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8gap"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8gap is ON HOLD  until Paper Publication
+==Structure of LARP7 protein p65-telomerase RNA complex in telomerase==
+<StructureSection load='8gap' size='340' side='right'caption='[[8gap]], [[Resolution|resolution]] 3.80&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8gap]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Tetrahymena_thermophila Tetrahymena thermophila] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8GAP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8GAP FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.8&#8491;</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=8gap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8gap OCA], [https://pdbe.org/8gap PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8gap RCSB], [https://www.ebi.ac.uk/pdbsum/8gap PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8gap ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/TERT_TETTS 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).<ref>PMID:10944124</ref> <ref>PMID:15696174</ref> <ref>PMID:16462747</ref> <ref>PMID:17322903</ref> <ref>PMID:20713447</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+La-related protein 7 (LARP7) are a family of RNA chaperones that protect the 3'-end of RNA and are components of specific ribonucleoprotein complexes (RNP). In Tetrahymena thermophila telomerase, LARP7 protein p65 together with telomerase reverse transcriptase (TERT) and telomerase RNA (TER) form the core RNP. p65 has four known domains-N-terminal domain (NTD), La motif (LaM), RNA recognition motif 1 (RRM1), and C-terminal xRRM2. To date, only the xRRM2 and LaM and their interactions with TER have been structurally characterized. Conformational dynamics leading to low resolution in cryo-EM density maps have limited our understanding of how full-length p65 specifically recognizes and remodels TER for telomerase assembly. Here, we combined focused classification of Tetrahymena telomerase cryo-EM maps with NMR spectroscopy to determine the structure of p65-TER. Three previously unknown helices are identified, one in the otherwise intrinsically disordered NTD that binds the La module, one that extends RRM1, and another preceding xRRM2, that stabilize p65-TER interactions. The extended La module (alphaN, LaM and RRM1) interacts with the four 3' terminal U nucleotides, while LaM and alphaN additionally interact with TER pseudoknot, and LaM with stem 1 and 5' end. Our results reveal the extensive p65-TER interactions that promote TER 3'-end protection, TER folding, and core RNP assembly and stabilization. The structure of full-length p65 with TER also sheds light on the biological roles of genuine La and LARP7 proteins as RNA chaperones and core RNP components.
-Authors:
+Structure of LARP7 Protein p65-telomerase RNA Complex in Telomerase Revealed by Cryo-EM and NMR.,Wang Y, He Y, Wang Y, Yang Y, Singh M, Eichhorn CD, Cheng X, Xiao Jiang Y, Hong Zhou Z, Feigon J J Mol Biol. 2023 Mar 20:168044. doi: 10.1016/j.jmb.2023.168044. PMID:37330293<ref>PMID:37330293</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 8gap" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Synthetic construct]]
+[[Category: Tetrahymena thermophila]]
+[[Category: Eichhorn CD]]
+[[Category: Feigon J]]
+[[Category: He Y]]
+[[Category: Singh M]]
+[[Category: Wang Y]]
+[[Category: Yang Y]]
+[[Category: Zhou ZH]]

8gap

From Proteopedia

Revision as of 21:19, 28 June 2023

Structure of LARP7 protein p65-telomerase RNA complex in telomerase

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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