5jmv

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Structure of a tRNA modification complex

Structural highlights

5jmv is a 8 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[KAE1B_METJA] Required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in tRNAs that read codons beginning with adenine. Is a 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. The Kae1 domain likely plays a direct catalytic role in this reaction (By similarity). The Bud32 domain probably displays kinase activity that regulates Kae1 function. In vitro, exhibits low ATPase activity, but does not bind DNA and does not have endonuclease activity.[HAMAP-Rule:MF_01447]^[1]

Publication Abstract from PubMed

KEOPS is an ancient protein complex required for the biosynthesis of N6-threonylcarbamoyladenosine (t6A), a universally conserved tRNA modification found on all ANN-codon recognizing tRNAs. KEOPS consist minimally of four essential subunits, namely the proteins Kae1, Bud32, Cgi121 and Pcc1, with yeast possessing the fifth essential subunit Gon7. Bud32, Cgi121, Pcc1 and Gon7 appear to have evolved to regulate the central t6A biosynthesis function of Kae1, but their precise function and mechanism of action remains unclear. Pcc1, in particular, binds directly to Kae1 and by virtue of its ability to form dimers in solution and in crystals, Pcc1 was inferred to function as a dimerization module for Kae1 and therefore KEOPS. We now present a 3.4 A crystal structure of a dimeric Kae1-Pcc1 complex providing direct evidence that Pcc1 can bind and dimerize Kae1. Further biophysical analysis of a complete archaeal KEOPS complex reveals that Pcc1 facilitates KEOPS dimerization in vitro Interestingly, while Pcc1-mediated dimerization of KEOPS is required to support the growth of yeast, it is dispensable for t6A biosynthesis by archaeal KEOPS in vitro, raising the question of how precisely Pcc1-mediated dimerization impacts cellular biology.

Structural and functional characterization of KEOPS dimerization by Pcc1 and its role in t6A biosynthesis.,Wan LC, Pillon MC, Thevakumaran N, Sun Y, Chakrabartty A, Guarne A, Kurinov I, Durocher D, Sicheri F Nucleic Acids Res. 2016 Jun 14. pii: gkw542. PMID:27302132^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Mao DY, Neculai D, Downey M, Orlicky S, Haffani YZ, Ceccarelli DF, Ho JS, Szilard RK, Zhang W, Ho CS, Wan L, Fares C, Rumpel S, Kurinov I, Arrowsmith CH, Durocher D, Sicheri F. Atomic structure of the KEOPS complex: an ancient protein kinase-containing molecular machine. Mol Cell. 2008 Oct 24;32(2):259-75. PMID:18951093 doi:10.1016/j.molcel.2008.10.002
↑ Wan LC, Pillon MC, Thevakumaran N, Sun Y, Chakrabartty A, Guarne A, Kurinov I, Durocher D, Sicheri F. Structural and functional characterization of KEOPS dimerization by Pcc1 and its role in t6A biosynthesis. Nucleic Acids Res. 2016 Jun 14. pii: gkw542. PMID:27302132 doi:http://dx.doi.org/10.1093/nar/gkw542