7kjt
From Proteopedia
KEOPS tRNA modifying sub-complex of archaeal Cgi121 and tRNA
Structural highlights
FunctionCG121_METJA Component of the KEOPS complex that is probably involved in the transfer of the threonylcarbamoyl moiety of threonylcarbamoyl-AMP (TC-AMP) to the N6 group of A37, a step in the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in tRNAs that read codons beginning with adenine. Cgi121 stimulates Bud32 kinase activity via an activation of Bud32 autophosphorylation.[1] Publication Abstract from PubMedThe 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 N(6)-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. A substrate binding model for the KEOPS tRNA modifying complex.,Beenstock J, Ona SM, Porat J, Orlicky S, Wan LCK, Ceccarelli DF, Maisonneuve P, Szilard RK, Yin Z, Setiaputra D, Mao DYL, Khan M, Raval S, Schriemer DC, Bayfield MA, Durocher D, Sicheri F Nat Commun. 2020 Dec 4;11(1):6233. doi: 10.1038/s41467-020-19990-5. PMID:33277478[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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