Project Details
Projekt
Functional and Structural Analysis of the 18S rRNA aminocarboxypropyl transferase Bam1
Subject Area
Biochemistry
Structural Biology
Structural Biology
Term
from 2015 to 2020
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 277406224
N1-methyl-N3-aminocarboxypropyl-pseudouridine is the chemically most complex modification occurring in eukaryotic small ribosomal subunit rRNA. Its biosynthesis from uridine requires three steps. The uridine to pseudouridine modification is catalyzed by a snoRNP guided by snR35. We previously showed that the SPOUT-class methyltransferase Nep1 introduces the N1-methyl group. Very recently we identified the enzyme that transfers the acp group to the N1-methylpseudouridine which we named Bam1. Here we propose to establish the structural and functional basis for the acp transferase activity of Bam1 and in particular to understand the structural prerequisites that allow Bam1 to utilize SAM as a substrate for acp transfer instead as a methyl group donor. Furthermore, we aim at understanding the catalytic mechanism of this reaction. The availability of knock-out and mutant strains for Bam1 in yeast will allow us to investigate the physiological relevance of this chemically complex modification and its importance in ribosome biogenesis. Due to the strong human homologies, our investigation could possibly also unravel new ribosomopathies, similar to the Bowen-Conradi syndrome observed for Nep1 catalysed N1-methylation.
DFG Programme
Priority Programmes
