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| | ==Est3 telomerase subunit in the yeast Hansenula polymorpha== | | ==Est3 telomerase subunit in the yeast Hansenula polymorpha== |
| - | <StructureSection load='6q44' size='340' side='right'caption='[[6q44]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='6q44' size='340' side='right'caption='[[6q44]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6q44]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Q44 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6Q44 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6q44]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Ogataea_parapolymorpha_DL-1 Ogataea parapolymorpha DL-1]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Q44 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Q44 FirstGlance]. <br> |
| - | </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=6q44 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6q44 OCA], [http://pdbe.org/6q44 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6q44 RCSB], [http://www.ebi.ac.uk/pdbsum/6q44 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6q44 ProSAT]</span></td></tr> | + | </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=6q44 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6q44 OCA], [https://pdbe.org/6q44 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6q44 RCSB], [https://www.ebi.ac.uk/pdbsum/6q44 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6q44 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/W1QJK4_OGAPD W1QJK4_OGAPD] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| - | Telomerase is a multisubunit ribonucleoprotein enzyme that is essential for continuous cellular proliferation. A key role of telomerase in cancer and ageing makes it a promising target for the development of cancer therapies and treatments of other age-associated diseases, since telomerase allows unlimited proliferation potential of cells in the majority of cancer types. However, the structure and molecular mechanism of telomerase action are still poorly understood. In budding yeast, telomerase consists of the catalytic subunit, the telomerase reverse transcriptase or Est2 protein, telomerase RNA (TLC1) and two regulatory subunits, Est1 and Est3. Each of the four subunits is essential for in vivo telomerase function. Est3 interacts directly with Est1 and Est2, and stimulates Est2 catalytic activity. However, the exact role of the Est3 protein in telomerase function is still unknown. Determination of the structure, dynamic and functional properties of Est3 can bring new insights into the molecular mechanism of telomerase activity. Here we report nearly complete (1)H, (13)C and (15)N resonance assignments of Est3 from the yeast Hansenula polymorpha. Analysis of the assigned chemical shifts allowed us to identify the protein's secondary structure and backbone dynamic properties. Structure-based sequence alignment revealed similarities in the structural organization of yeast Est3 and mammalian TPP1 proteins. | + | Telomerase is a ribonucleoprotein enzyme, which maintains genome integrity in eukaryotes and ensures continuous cellular proliferation. Telomerase holoenzyme from the thermotolerant yeast Hansenula polymorpha, in addition to the catalytic subunit (TERT) and telomerase RNA (TER), contains accessory proteins Est1 and Est3, which are essential for in vivo telomerase function. Here we report the high-resolution structure of Est3 from Hansenula polymorpha (HpEst3) in solution, as well as the characterization of its functional relationships with other components of telomerase. The overall structure of HpEst3 is similar to that of Est3 from Saccharomyces cerevisiae and human TPP1. We have shown that telomerase activity in H. polymorpha relies on both Est3 and Est1 proteins in a functionally symmetrical manner. The absence of either Est3 or Est1 prevents formation of a stable ribonucleoprotein complex, weakens binding of a second protein to TER, and decreases the amount of cellular TERT, presumably due to the destabilization of telomerase RNP. NMR probing has shown no direct in vitro interactions of free Est3 either with the N-terminal domain of TERT or with DNA or RNA fragments mimicking the probable telomerase environment. Our findings corroborate the idea that telomerase possesses the evolutionarily variable functionality within the conservative structural context. |
| | | | |
| - | Chemical shift assignments and the secondary structure of the Est3 telomerase subunit in the yeast Hansenula polymorpha.,Mariasina SS, Efimov SV, Petrova OA, Rodina EV, Malyavko AN, Zvereva MI, Klochkov VV, Dontsova OA, Polshakov VI Biomol NMR Assign. 2018 Apr;12(1):57-62. doi: 10.1007/s12104-017-9780-5. Epub, 2017 Sep 15. PMID:28916982<ref>PMID:28916982</ref>
| + | Insights into the structure and function of Est3 from the Hansenula polymorpha telomerase.,Shepelev NM, Mariasina SS, Mantsyzov AB, Malyavko AN, Efimov SV, Petrova OA, Rodina EV, Zvereva MI, Dontsova OA, Polshakov VI Sci Rep. 2020 Jul 6;10(1):11109. doi: 10.1038/s41598-020-68107-x. PMID:32632130<ref>PMID:32632130</ref> |
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| | 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> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Dontsova, O A]] | + | [[Category: Ogataea parapolymorpha DL-1]] |
| - | [[Category: Efimov, S V]] | + | [[Category: Dontsova OA]] |
| - | [[Category: Mantsyzov, A B]] | + | [[Category: Efimov SV]] |
| - | [[Category: Mariasina, S S]] | + | [[Category: Mantsyzov AB]] |
| - | [[Category: Petrova, O A]] | + | [[Category: Mariasina SS]] |
| - | [[Category: Polshakov, V I]] | + | [[Category: Petrova OA]] |
| - | [[Category: Est3]] | + | [[Category: Polshakov VI]] |
| - | [[Category: Ob-fold]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| - | [[Category: Telomerase]]
| + | |
| Structural highlights
Function
W1QJK4_OGAPD
Publication Abstract from PubMed
Telomerase is a ribonucleoprotein enzyme, which maintains genome integrity in eukaryotes and ensures continuous cellular proliferation. Telomerase holoenzyme from the thermotolerant yeast Hansenula polymorpha, in addition to the catalytic subunit (TERT) and telomerase RNA (TER), contains accessory proteins Est1 and Est3, which are essential for in vivo telomerase function. Here we report the high-resolution structure of Est3 from Hansenula polymorpha (HpEst3) in solution, as well as the characterization of its functional relationships with other components of telomerase. The overall structure of HpEst3 is similar to that of Est3 from Saccharomyces cerevisiae and human TPP1. We have shown that telomerase activity in H. polymorpha relies on both Est3 and Est1 proteins in a functionally symmetrical manner. The absence of either Est3 or Est1 prevents formation of a stable ribonucleoprotein complex, weakens binding of a second protein to TER, and decreases the amount of cellular TERT, presumably due to the destabilization of telomerase RNP. NMR probing has shown no direct in vitro interactions of free Est3 either with the N-terminal domain of TERT or with DNA or RNA fragments mimicking the probable telomerase environment. Our findings corroborate the idea that telomerase possesses the evolutionarily variable functionality within the conservative structural context.
Insights into the structure and function of Est3 from the Hansenula polymorpha telomerase.,Shepelev NM, Mariasina SS, Mantsyzov AB, Malyavko AN, Efimov SV, Petrova OA, Rodina EV, Zvereva MI, Dontsova OA, Polshakov VI Sci Rep. 2020 Jul 6;10(1):11109. doi: 10.1038/s41598-020-68107-x. PMID:32632130[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Shepelev NM, Mariasina SS, Mantsyzov AB, Malyavko AN, Efimov SV, Petrova OA, Rodina EV, Zvereva MI, Dontsova OA, Polshakov VI. Insights into the structure and function of Est3 from the Hansenula polymorpha telomerase. Sci Rep. 2020 Jul 6;10(1):11109. PMID:32632130 doi:10.1038/s41598-020-68107-x
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