The crystal structure of Nep1 reveals an extended SPOUT-class methyltransferase fold and a pre-organized SAM-binding site.

Nucleic Acids Research
Alexander B TaylorJens Wöhnert

Abstract

Ribosome biogenesis in eukaryotes requires the participation of a large number of ribosome assembly factors. The highly conserved eukaryotic nucleolar protein Nep1 has an essential but unknown function in 18S rRNA processing and ribosome biogenesis. In Saccharomyces cerevisiae the malfunction of a temperature-sensitive Nep1 protein (nep1-1(ts)) was suppressed by the addition of S-adenosylmethionine (SAM). This suggests the participation of Nep1 in a methyltransferase reaction during ribosome biogenesis. In addition, yeast Nep1 binds to a 6-nt RNA-binding motif also found in 18S rRNA and facilitates the incorporation of ribosomal protein Rps19 during the formation of pre-ribosomes. Here, we present the X-ray structure of the Nep1 homolog from the archaebacterium Methanocaldococcus jannaschii in its free form (2.2 A resolution) and bound to the S-adenosylmethionine analog S-adenosylhomocysteine (SAH, 2.15 A resolution) and the antibiotic and general methyltransferase inhibitor sinefungin (2.25 A resolution). The structure reveals a fold which is very similar to the conserved core fold of the SPOUT-class methyltransferases but contains a novel extension of this common core fold. SAH and sinefungin bind to Nep1 at a preformed bindi...Continue Reading

References

Jul 28, 1995·The Journal of Biological Chemistry·J A KowalakJ A McCloskey
Jun 1, 1995·Current Opinion in Cell Biology·T Mélèse, Z Xue
Jan 5, 1993·Journal of Molecular Biology·G D Van DuyneJ Clardy
Mar 21, 1998·Genes & Development·D L LafontaineD Tollervey
Feb 19, 1999·Science·T M Lowe, S R Eddy
Jul 8, 1999·Current Opinion in Cell Biology·U Scheer, R Hock
Oct 26, 1999·Acta Crystallographica. Section D, Biological Crystallography·J W Pflugrath
Nov 5, 1999·Trends in Biochemical Sciences·J R Warner
Oct 3, 2000·Nature·B T WimberlyV Ramakrishnan
Jun 22, 2002·Acta Crystallographica. Section D, Biological Crystallography·Osamu NurekiShigeyuki Yokoyama
Jul 13, 2002·Trends in Biochemical Sciences·Wayne A Decatur, Maurille J Fournier
Oct 24, 2002·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsThomas C Terwilliger
Dec 31, 2002·Current Opinion in Structural Biology·Jennifer L Martin, Fiona M McMillan
May 30, 2003·The EMBO Journal·Hyung Jun AhnJin Kuk Yang
Jul 11, 2003·The EMBO Journal·Irene M A Nooren, Janet M Thornton
Sep 6, 2003·Gene·Micheline Fromont-RacineFranco Fasiolo
Oct 30, 2003·Journal of Molecular Biology·Patricia A ElkinsWalter M Holmes
Jan 21, 2004·Molecular Cell·Carme FabregaChristopher D Lima
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Jan 8, 2005·The Journal of Biological Chemistry·Kazunori WatanabeHiroyuki Hori
Mar 3, 2006·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Elizabeth PlesheRobert T Batey
May 25, 2006·Molecular Genetics and Genomics : MGG·Markus BuchhauptKarl-Dieter Entian
Sep 9, 2006·Science·Maria SelmerV Ramakrishnan
Dec 19, 2006·Methods in Molecular Biology·Clemens VonrheinGérard Bricogne
Mar 7, 2007·BMC Bioinformatics·Karolina L TkaczukJanusz M Bujnicki

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Citations

Sep 23, 2010·BMC Developmental Biology·Xiaoli WuHao Ding
Nov 26, 2010·Journal of Molecular Cell Biology·Hong-Ying Chen, Y Adam Yuan
Sep 5, 2013·Proceedings of the National Academy of Sciences of the United States of America·Ute A HellmichJens Wöhnert
Dec 14, 2011·Nucleic Acids Research·Thomas VeithEnrico Schleiff
Jun 29, 2010·Epigenomics·Tanya Petrossian, Steven Clarke
Jul 18, 2015·Proceedings of the National Academy of Sciences of the United States of America·Takuhiro ItoShigeyuki Yokoyama
Oct 26, 2012·The FEBS Journal·Jason K K Low, Marc R Wilkins
Sep 28, 2015·Trends in Biochemical Sciences·Sunny Sharma, Denis L J Lafontaine
Nov 25, 2016·The Journal of Biological Chemistry·Yong ZhangAngelika Gründling
May 26, 2009·American Journal of Human Genetics·Joy ArmisteadBarbara Triggs-Raine

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Methods Mentioned

BETA
3-hybrid
X-ray
PCR
gel filtration
three-hybrid

Software Mentioned

DM
DALI
2000
COOT
SHARP
PHENIX
autoSHARP
HKL
TREK

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