The symbol, UniProt record and literature agree. QRSL1 is human GatA, the catalytic amidase subunit of the mitochondrial GatCAB complex. It belongs to the amidase family, GatA subfamily, and carries the Amidase domain (PF01425, IPR000120) and the GatA signature (IPR004412). The 2009 paper that defined the human complex calls the protein hGatA, which is the name used in the UniProt record (PMID:19805282). I found no conflicting literature for a different gene under this symbol. I did not read the full text of the papers cited below, so the points taken from them rest on abstracts and search summaries, not on checked quotations.
Reaction (EC 3.5.1.2 per UniProt/HAMAP): the enzyme performs the second step of an indirect route to Gln-tRNA(Gln) in mitochondria.
- Mitochondria have no glutaminyl-tRNA synthetase. Mitochondrial GluRS (EARS2) misacylates mt-tRNA(Gln) with glutamate, giving Glu-tRNA(Gln).
- GatCAB then converts Glu-tRNA(Gln) to Gln-tRNA(Gln) by ATP-dependent transamidation: Glu-tRNA(Gln) + ATP + glutamine → Gln-tRNA(Gln) + glutamate + ADP + Pi.
- GatA hydrolyses glutamine to ammonia. The ammonia is channelled to GatB, which activates the misacylated glutamate with ATP and then amidates it.
- Nagao et al. (2009) identified hGatCAB, showed that GluRS misacylates mt-tRNA(Gln), and reconstituted Gln-tRNA(Gln) formation in vitro with recombinant enzymes (PMID:19805282; PMC2752530). The same paper reported:
- Knockdown of hGatCAB subunits caused accumulation of Glu-charged tRNA and respiration defects.
- The misacylated tRNA binds weakly to mtEF-Tu, which the authors interpret as a quality-control step for translational accuracy.
- The other two subunits are GATB (PET112) and GATC. Together with QRSL1 they form a heterotrimer.
- The amidase fold, the catalytic Ser-Ser-Lys triad typical of the family, and the bacterial GatCAB mechanism are my own inference from the family assignment. I did not check them against a structure or publication here.
Substrate specificity: the substrate is mt-tRNA(Gln) misacylated with Glu. Human mitochondria use this route for the single mt-tRNA(Gln) species. Glutamine is the nitrogen donor.
The enzyme is a mitochondrial matrix protein. The "mitochondrial" and "GatCAB complex" annotations come from the 2009 characterisation in human cells (PMID:19805282). It acts in the matrix, next to the mitochondrial translation machinery.
It sits in mitochondrial translation. EARS2 misacylates tRNA(Gln), GatCAB corrects it, and mtEF-Tu delivers the correct Gln-tRNA(Gln) to the ribosome. This makes GatCAB necessary for translating the mtDNA-encoded OXPHOS subunits, and loss of it reduces respiratory-chain function.
Friederich et al. 2018, Nat Commun (doi:10.1038/s41467-018-06250-w; I could not confirm the PMID), reported:
- Nine patients from five families with defects in a GatCAB subunit (QRSL1, GATB or GATC).
- A lethal metabolic cardiomyopathy syndrome in these patients.
- Combined respiratory chain enzyme deficiencies.
- Deficient mt-tRNA(Gln) charging and mitochondrial translation in patient fibroblasts without glutamine.
- Confirmation of pathogenicity by lentiviral rescue and by yeast modelling.
- Sources: Bioblast summary; related title.
NCBI links QRSL1 to combined oxidative phosphorylation deficiency 40 (NCBI Gene 76563).
| Claim | Evidence |
|---|---|
| Part of the mitochondrial GatCAB complex that makes Gln-tRNA(Gln) | Experimental: reconstitution and knockdown (PMID:19805282) |
| Amidase and glutamine-hydrolysing activity | Inferred from family and domain assignment (UniProt/HAMAP) |
| Required for mitochondrial translation in humans | Patient and rescue data (Friederich 2018) |