| Structural highlights
Function
[BUD32_YEAST] Component of the EKC/KEOPS complex that is required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in tRNAs that read codons beginning with adenine. The complex is probably involved in the transfer of the threonylcarbamoyl moiety of threonylcarbamoyl-AMP (TC-AMP) to the N6 group of A37. BUD32 has ATPase activity in the context of the EKC/KEOPS complex and likely plays a supporting role to the catalytic subunit KAE1. The EKC/KEOPS complex also promotes both telomere uncapping and telomere elongation. The complex is required for efficient recruitment of transcriptional coactivators. Important for bud site selection.[1] [2] [3] [4] [5] [6] [CG121_YEAST] Component of the EKC/KEOPS complex that is required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in tRNAs that read codons beginning with adenine. The complex is probably involved in the transfer of the threonylcarbamoyl moiety of threonylcarbamoyl-AMP (TC-AMP) to the N6 group of A37. CGI121 acts as an allosteric effector that regulates the t(6)A activity of the complex. The EKC/KEOPS complex also promotes both telomere uncapping and telomere elongation. The complex is required for efficient recruitment of transcriptional coactivators. CGI121 is not required for tRNA modification.[7] [8] [9] [10] [11] [12]
Publication Abstract from PubMed
The yeast KEOPS protein complex comprising Kae1, Bud32, Cgi121, Pcc1 and Gon7 is responsible for the essential tRNA threonylcarbamoyladenosine (t6A) modification. Deletion of genes coding for the KEOPS subunits also affects telomere elongation and transcriptional regulation. In the present work, the crystal structure of Bud32/Cgi121 in complex with ADP revealed that ADP is bound in the catalytic site of Bud32 in a canonical manner characteristic of Protein Kinase A (PKA) family proteins. We found that Gon7 forms a stable heterodimer with Pcc1 and report the crystal structure of the Pcc1-Gon7 heterodimer. Gon7 interacts with the same Pcc1 region engaged in the archaeal Pcc1 homodimer. We further show that yeast KEOPS, unlike its archaeal counterpart, exists as a heteropentamer in which Gon7, Pcc1, Kae1, Bud32 and Cgi121 also adopt a linear arrangement. We constructed a model of yeast KEOPS that provides structural insight into the role of Gon7. The model also revealed the presence of a highly positively charged crater surrounding the entrance of Kae1 that likely binds tRNA.
Crystal structures of the Gon7/Pcc1 and Bud32/Cgi121 complexes provide a model for the complete yeast KEOPS complex.,Zhang W, Collinet B, Graille M, Daugeron MC, Lazar N, Libri D, Durand D, van Tilbeurgh H Nucleic Acids Res. 2015 Mar 3. pii: gkv155. PMID:25735745[13]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Downey M, Houlsworth R, Maringele L, Rollie A, Brehme M, Galicia S, Guillard S, Partington M, Zubko MK, Krogan NJ, Emili A, Greenblatt JF, Harrington L, Lydall D, Durocher D. A genome-wide screen identifies the evolutionarily conserved KEOPS complex as a telomere regulator. Cell. 2006 Mar 24;124(6):1155-68. PMID:16564010 doi:http://dx.doi.org/S0092-8674(06)00198-X
- ↑ Kisseleva-Romanova E, Lopreiato R, Baudin-Baillieu A, Rousselle JC, Ilan L, Hofmann K, Namane A, Mann C, Libri D. Yeast homolog of a cancer-testis antigen defines a new transcription complex. EMBO J. 2006 Aug 9;25(15):3576-85. Epub 2006 Jul 27. PMID:16874308 doi:http://dx.doi.org/10.1038/sj.emboj.7601235
- ↑ Srinivasan M, Mehta P, Yu Y, Prugar E, Koonin EV, Karzai AW, Sternglanz R. The highly conserved KEOPS/EKC complex is essential for a universal tRNA modification, t6A. EMBO J. 2011 Mar 2;30(5):873-81. doi: 10.1038/emboj.2010.343. Epub 2010 Dec 24. PMID:21183954 doi:10.1038/emboj.2010.343
- ↑ Daugeron MC, Lenstra TL, Frizzarin M, El Yacoubi B, Liu X, Baudin-Baillieu A, Lijnzaad P, Decourty L, Saveanu C, Jacquier A, Holstege FC, de Crecy-Lagard V, van Tilbeurgh H, Libri D. Gcn4 misregulation reveals a direct role for the evolutionary conserved EKC/KEOPS in the t6A modification of tRNAs. Nucleic Acids Res. 2011 Aug;39(14):6148-60. doi: 10.1093/nar/gkr178. Epub 2011, Apr 1. PMID:21459853 doi:http://dx.doi.org/10.1093/nar/gkr178
- ↑ Perrochia L, Crozat E, Hecker A, Zhang W, Bareille J, Collinet B, van Tilbeurgh H, Forterre P, Basta T. In vitro biosynthesis of a universal t6A tRNA modification in Archaea and Eukarya. Nucleic Acids Res. 2013 Feb 1;41(3):1953-64. doi: 10.1093/nar/gks1287. Epub 2012 , Dec 20. PMID:23258706 doi:http://dx.doi.org/10.1093/nar/gks1287
- ↑ Wan LC, Mao DY, Neculai D, Strecker J, Chiovitti D, Kurinov I, Poda G, Thevakumaran N, Yuan F, Szilard RK, Lissina E, Nislow C, Caudy AA, Durocher D, Sicheri F. Reconstitution and characterization of eukaryotic N6-threonylcarbamoylation of tRNA using a minimal enzyme system. Nucleic Acids Res. 2013 Apr 25. PMID:23620299 doi:10.1093/nar/gkt322
- ↑ Downey M, Houlsworth R, Maringele L, Rollie A, Brehme M, Galicia S, Guillard S, Partington M, Zubko MK, Krogan NJ, Emili A, Greenblatt JF, Harrington L, Lydall D, Durocher D. A genome-wide screen identifies the evolutionarily conserved KEOPS complex as a telomere regulator. Cell. 2006 Mar 24;124(6):1155-68. PMID:16564010 doi:http://dx.doi.org/S0092-8674(06)00198-X
- ↑ Kisseleva-Romanova E, Lopreiato R, Baudin-Baillieu A, Rousselle JC, Ilan L, Hofmann K, Namane A, Mann C, Libri D. Yeast homolog of a cancer-testis antigen defines a new transcription complex. EMBO J. 2006 Aug 9;25(15):3576-85. Epub 2006 Jul 27. PMID:16874308 doi:http://dx.doi.org/10.1038/sj.emboj.7601235
- ↑ Srinivasan M, Mehta P, Yu Y, Prugar E, Koonin EV, Karzai AW, Sternglanz R. The highly conserved KEOPS/EKC complex is essential for a universal tRNA modification, t6A. EMBO J. 2011 Mar 2;30(5):873-81. doi: 10.1038/emboj.2010.343. Epub 2010 Dec 24. PMID:21183954 doi:10.1038/emboj.2010.343
- ↑ Daugeron MC, Lenstra TL, Frizzarin M, El Yacoubi B, Liu X, Baudin-Baillieu A, Lijnzaad P, Decourty L, Saveanu C, Jacquier A, Holstege FC, de Crecy-Lagard V, van Tilbeurgh H, Libri D. Gcn4 misregulation reveals a direct role for the evolutionary conserved EKC/KEOPS in the t6A modification of tRNAs. Nucleic Acids Res. 2011 Aug;39(14):6148-60. doi: 10.1093/nar/gkr178. Epub 2011, Apr 1. PMID:21459853 doi:http://dx.doi.org/10.1093/nar/gkr178
- ↑ Perrochia L, Crozat E, Hecker A, Zhang W, Bareille J, Collinet B, van Tilbeurgh H, Forterre P, Basta T. In vitro biosynthesis of a universal t6A tRNA modification in Archaea and Eukarya. Nucleic Acids Res. 2013 Feb 1;41(3):1953-64. doi: 10.1093/nar/gks1287. Epub 2012 , Dec 20. PMID:23258706 doi:http://dx.doi.org/10.1093/nar/gks1287
- ↑ Wan LC, Mao DY, Neculai D, Strecker J, Chiovitti D, Kurinov I, Poda G, Thevakumaran N, Yuan F, Szilard RK, Lissina E, Nislow C, Caudy AA, Durocher D, Sicheri F. Reconstitution and characterization of eukaryotic N6-threonylcarbamoylation of tRNA using a minimal enzyme system. Nucleic Acids Res. 2013 Apr 25. PMID:23620299 doi:10.1093/nar/gkt322
- ↑ Zhang W, Collinet B, Graille M, Daugeron MC, Lazar N, Libri D, Durand D, van Tilbeurgh H. Crystal structures of the Gon7/Pcc1 and Bud32/Cgi121 complexes provide a model for the complete yeast KEOPS complex. Nucleic Acids Res. 2015 Mar 3. pii: gkv155. PMID:25735745 doi:http://dx.doi.org/10.1093/nar/gkv155
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