A substrate binding model for the KEOPS tRNA modifying complex

Jonah Beenstock, Samara Mishelle Ona, Jennifer Porat, Stephen Orlicky, Leo C. K. Wan, Derek F. Ceccarelli, Pierre Maisonneuve, Rachel K. Szilard, Zhe Yin, Dheva Setiaputra, Daniel Y. L. Mao, Morgan Khan, Shaunak Raval, David C. Schriemer, Mark A. Bayfield, Daniel Durocher and Frank Sicheri ()
Additional contact information
Jonah Beenstock: Mount Sinai Hospital
Samara Mishelle Ona: Mount Sinai Hospital
Jennifer Porat: York University
Stephen Orlicky: Mount Sinai Hospital
Leo C. K. Wan: Mount Sinai Hospital
Derek F. Ceccarelli: Mount Sinai Hospital
Pierre Maisonneuve: Mount Sinai Hospital
Rachel K. Szilard: Mount Sinai Hospital
Zhe Yin: Mount Sinai Hospital
Dheva Setiaputra: Mount Sinai Hospital
Daniel Y. L. Mao: Mount Sinai Hospital
Morgan Khan: University of Calgary
Shaunak Raval: University of Calgary
David C. Schriemer: University of Calgary
Mark A. Bayfield: York University
Daniel Durocher: Mount Sinai Hospital
Frank Sicheri: Mount Sinai Hospital

Nature Communications, 2020, vol. 11, issue 1, 1-17

Abstract: Abstract The KEOPS complex, which is conserved across archaea and eukaryotes, is composed of four core subunits; Pcc1, Kae1, Bud32 and Cgi121. KEOPS is crucial for the fitness of all organisms examined. In humans, pathogenic mutations in KEOPS genes lead to Galloway–Mowat syndrome, an autosomal-recessive disease causing childhood lethality. Kae1 catalyzes the universal and essential tRNA modification N6-threonylcarbamoyl adenosine, but the precise roles of all other KEOPS subunits remain an enigma. Here we show using structure-guided studies that Cgi121 recruits tRNA to KEOPS by binding to its 3’ CCA tail. A composite model of KEOPS bound to tRNA reveals that all KEOPS subunits form an extended tRNA-binding surface that we have validated in vitro and in vivo to mediate the interaction with the tRNA substrate and its modification. These findings provide a framework for understanding the inner workings of KEOPS and delineate why all KEOPS subunits are essential.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-19990-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19990-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-19990-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().