4qtt

Structure of S. cerevisiae Bud23-Trm112 complex involved in formation of m7G1575 on 18S rRNA (apo-form)

spinqualitylabelsall models 4qtt, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4qtt is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 12P, EDO, ZN NonStd Res: CSO Related: 4qtm, 4qtu Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [TR112_YEAST] Together with MTQ2, required for the methylation of eRF1 on 'Gln-182'. Together with TRM11, required for the formation of 2-methylguanosine at position 10 in tRNA. Probably has additional functions. [BUD23_YEAST] S-adenosyl-L-methionine-dependent methyltransferase that specifically methylates the N(7) position of guanine 1575 (m7G1575) in 18S rRNA. Requires the methyltransferase adapter protein TRM112 for full rRNA methyltransferase activity. Important for biogenesis end export of the 40S ribosomal subunit independent on its methyltransferase activity. Required for efficient cleavage of the primary 35S precursor rRNA at site A2. Involved in positioning the proximal bud pole signal. Publication Abstract from PubMed The eukaryotic small ribosomal subunit carries only four ribosomal (r) RNA methylated bases, all close to important functional sites. N7-methylguanosine (m7G) introduced at position 1575 on 18S rRNA by Bud23-Trm112 is at a ridge forming a steric block between P- and E-site tRNAs. Here we report atomic resolution structures of Bud23-Trm112 in the apo and S-adenosyl-l-methionine (SAM)-bound forms. Bud23 and Trm112 interact through formation of a beta-zipper involving main-chain atoms, burying an important hydrophobic surface and stabilizing the complex. The structures revealed that the coactivator Trm112 undergoes an induced fit to accommodate its methyltransferase (MTase) partner. We report important structural similarity between the active sites of Bud23 and Coffea canephora xanthosine MTase, leading us to propose and validate experimentally a model for G1575 coordination. We identify Bud23 residues important for Bud23-Trm112 complex formation and recruitment to pre-ribosomes. We report that though Bud23-Trm112 binds precursor ribosomes at an early nucleolar stage, m7G methylation occurs at a late step of small subunit biogenesis, implying specifically delayed catalytic activation. Finally, we show that Bud23-Trm112 interacts directly with the box C/D snoRNA U3-associated DEAH RNA helicase Dhr1 supposedly involved in central pseudoknot formation; this suggests that Bud23-Trm112 might also contribute to controlling formation of this irreversible and dramatic structural reorganization essential to overall folding of small subunit rRNA. Our study contributes important new elements to our understanding of key molecular aspects of human ribosomopathy syndromes associated with WBSCR22 (human Bud23) malfunction. Structural and functional studies of Bud23-Trm112 reveal 18S rRNA N7-G1575 methylation occurs on late 40S precursor ribosomes.,Letoquart J, Huvelle E, Wacheul L, Bourgeois G, Zorbas C, Graille M, Heurgue-Hamard V, Lafontaine DL Proc Natl Acad Sci U S A. 2014 Dec 8. pii: 201413089. PMID:25489090 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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