The GidA associated domain 3 is a motif that has been identified at the C-terminus of protein GidA. It consists of 4 helices, the last three being rather short and forming small bundle at the top end of the first longer one. It is here named helical domain 3 because in GidA it is preceded by two other C-terminal helical domain (based on crystal structures PMID:18565343, 19446527). GidA is an tRNA modification enzyme found in bacteria and mitochondrial. Based on mutational analysis this domain has been suggested to be implicated in binding of the D-stem of tRNA (PMID:19446527) and to be responsible for the interaction with protein MnmE PMID:18565343. Structures of GidA in complex with either tRNA or MnmE are missing. Reported to bind to Pfam family MnmE, PF12631.
Family alignment:
There are 18150 GIDA_assoc_3 domains in 18150 proteins in SMART's nrdb database.
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Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing GIDA_assoc_3 domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with GIDA_assoc_3 domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing GIDA_assoc_3 domain in the selected taxonomic class.
Conserved cysteine residues of GidA are essential for biogenesis of5-carboxymethylaminomethyluridine at tRNA anticodon.
Structure. 2009; 17: 713-24
Display abstract
The 5-carboxymethylaminomethyl modification of uridine (cmnm(5)U) at theanticodon first position occurs in tRNAs that read split codon boxes ending with purine. This modification is crucial for correct translation, by restrictingcodon-anticodon wobbling. Two conserved enzymes, GidA and MnmE, participate inthe cmnm(5)U modification process. Here we determined the crystal structure ofAquifex aeolicus GidA at 2.3 A resolution. The structure revealed the tightinteraction of GidA with FAD. Structure-based mutation analyses allowed us toidentify two conserved Cys residues in the vicinity of the FAD-binding site that are essential for the cmnm(5)U modification in vivo. Together with mutationalanalysis of MnmE, we propose a mechanism for the cmnm(5)U modification processwhere GidA, but not MnmE, attacks the C6 atom of uridine by a mechanism analogousto that of thymidylate synthase. We also present a tRNA-docking model thatprovides structural insights into the tRNA recognition mechanism for efficientmodification.
Crystal structures of the conserved tRNA-modifying enzyme GidA: implications for its interaction with MnmE and substrate.
J Mol Biol. 2008; 380: 532-47
Display abstract
GidA is a flavin-adenine-dinucleotide (FAD)-binding protein that is conservedamong bacteria and eucarya. Together with MnmE, it is involved in the addition ofa carboxymethylaminomethyl group to the uridine base in the wobble position(nucleotide 34) of tRNAs that read split codon boxes. Here, we report the crystalstructures of the GidA proteins from both Escherichia coli and Chlorobiumtepidum. The structures show that the protein can be divided into three domains: a first FAD-binding domain showing the classical Rossmann fold, a secondalpha/beta domain inserted between two strands of the Rossmann fold, and analpha-helical C-terminal domain. The domain inserted into the Rossmann folddisplays structural similarity to thenicotinamide-adenine-dinucleotide-(phosphate)-binding domains of phenolhydroxylase and 3-hydroxy-3-methylglutaryl-CoA reductase, and, correspondingly,we show that GidA binds NADH with high specificity as an initial donor ofelectrons. GidA behaves as a homodimer in solution. As revealed by the crystalstructures, homodimerization is mediated via both the FAD-binding domain and the NADH-binding domain. Finally, a large patch of highly conserved, positivelycharged residues on the surface of GidA leading to the FAD-binding site suggests a tRNA-binding surface. We propose a model for the interaction between GidA andMnmE, which is supported by site-directed mutagenesis. Our data suggest that thisinteraction is modulated and potentially regulated by the switch function of the G domain of MnmE.
