Structural highlights
Function
[EST3_YEAST] Component of the telomerase complex involved in telomere replication. Stimulates RNA/DNA heteroduplex unwinding which favors the telomere replication by the telomerase.[1] [2] [3] [4] [5] [6]
Publication Abstract from PubMed
Telomerase is essential for continuous cellular proliferation. Substantial insights have come from studies of budding yeast telomerase, which consists of a catalytic core in association with two regulatory proteins, ever shorter telomeres 1 and 3 (Est1 and Est3). We report here a high-resolution structure of the Est3 telomerase subunit determined using a recently developed strategy that combines minimal NMR experimental data with Rosetta de novo structure prediction algorithms. Est3 adopts an overall protein fold which is structurally similar to that adopted by the shelterin component TPP1. However, the characteristics of the surface of the experimentally determined Est3 structure are substantially different from those predicted by prior homology-based models of Est3. Structure-guided mutagenesis of the complete surface of the Est3 protein reveals two adjacent patches on a noncanonical face of the protein that differentially mediate telomere function. Mapping these two patches on the Est3 structure defines a set of shared features between Est3 and HsTPP1, suggesting an analogous multifunctional surface on TPP1.
Structure of Est3 reveals a bimodal surface with differential roles in telomere replication.,Rao T, Lubin JW, Armstrong GS, Tucey TM, Lundblad V, Wuttke DS Proc Natl Acad Sci U S A. 2014 Jan 7;111(1):214-8. doi: 10.1073/pnas.1316453111. , Epub 2013 Dec 16. PMID:24344315[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lendvay TS, Morris DK, Sah J, Balasubramanian B, Lundblad V. Senescence mutants of Saccharomyces cerevisiae with a defect in telomere replication identify three additional EST genes. Genetics. 1996 Dec;144(4):1399-412. PMID:8978029
- ↑ Morris DK, Lundblad V. Programmed translational frameshifting in a gene required for yeast telomere replication. Curr Biol. 1997 Dec 1;7(12):969-76. PMID:9382847
- ↑ Lingner J, Cech TR, Hughes TR, Lundblad V. Three Ever Shorter Telomere (EST) genes are dispensable for in vitro yeast telomerase activity. Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11190-5. PMID:9326584
- ↑ Diede SJ, Gottschling DE. Telomerase-mediated telomere addition in vivo requires DNA primase and DNA polymerases alpha and delta. Cell. 1999 Dec 23;99(7):723-33. PMID:10619426
- ↑ Sharanov YS, Zvereva MI, Dontsova OA. Saccharomyces cerevisiae telomerase subunit Est3p binds DNA and RNA and stimulates unwinding of RNA/DNA heteroduplexes. FEBS Lett. 2006 Aug 21;580(19):4683-90. Epub 2006 Jul 24. PMID:16884717 doi:http://dx.doi.org/10.1016/j.febslet.2006.07.048
- ↑ Yang CP, Chen YB, Meng FL, Zhou JQ. Saccharomyces cerevisiae Est3p dimerizes in vitro and dimerization contributes to efficient telomere replication in vivo. Nucleic Acids Res. 2006 Jan 17;34(2):407-16. Print 2006. PMID:16418502 doi:http://dx.doi.org/10.1093/nar/gkj445
- ↑ Rao T, Lubin JW, Armstrong GS, Tucey TM, Lundblad V, Wuttke DS. Structure of Est3 reveals a bimodal surface with differential roles in telomere replication. Proc Natl Acad Sci U S A. 2014 Jan 7;111(1):214-8. doi: 10.1073/pnas.1316453111. , Epub 2013 Dec 16. PMID:24344315 doi:http://dx.doi.org/10.1073/pnas.1316453111
