Crystal structures of the Gon7/Pcc1 and Bud32/Cgi121 complexes provide a model for the complete yeast KEOPS complex

Nucleic Acids Research
Wenhua ZhangHerman van Tilbeurgh

Abstract

The yeast KEOPS protein complex comprising Kae1, Bud32, Cgi121, Pcc1 and Gon7 is responsible for the essential tRNA threonylcarbamoyladenosine (t(6)A) 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.

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Citations

Sep 5, 2015·Molecular Microbiology·Patrick C ThiavilleValérie de Crécy-Lagard
Jan 9, 2018·Nucleic Acids Research·Amit LuthraManal A Swairjo
Aug 15, 2017·Nature Genetics·Daniela A BraunFriedhelm Hildebrandt
Sep 5, 2019·Nature Communications·Christelle ArrondelGéraldine Mollet
Feb 13, 2020·Nucleic Acids Research·Jing-Bo ZhouXiao-Long Zhou
Apr 3, 2019·Nucleic Acids Research·Ming-Hong HeJin-Qiu Zhou
Mar 16, 2017·Acta Crystallographica. Section D, Structural Biology·Daria A BeshnovaVictor S Lamzin
Dec 26, 2019·Scientific Reports·Vivek Modi, Roland L Dunbrack
Dec 6, 2020·Nature Communications·Jonah BeenstockFrank Sicheri
Feb 7, 2021·Communications Biology·Jian LiZigang Dong
Oct 7, 2021·Nucleic Acids Research·Jonah Beenstock, Frank Sicheri

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Methods Mentioned

BETA
PCR
size-exclusion chromatography
X-ray
light scattering
nuclear magnetic resonance
gel filtration
NMR

Software Mentioned

COOT
WARP
REFMAC5
OmniSEC
Phaser
CRYSOL
PD2
ARP
PatchDock
PHENIX

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