AI Article Synopsis
- N-threonyl-carbamoylation of adenosine 37 in ANN-type tRNAs is crucial for accurate protein translation, utilizing the YRDC and OSGEP enzymes.
- Mutations in the KEOPS complex subunits have been linked to Galloway-Mowat syndrome, with YRDC mutations causing severe symptoms and GON7 mutations resulting in milder forms.
- The crystal structure of a GON7 subcomplex reveals that GON7 becomes partially structured when interacting with LAGE3, indicating its role in stabilizing the KEOPS complex.
Article Abstract
N-threonyl-carbamoylation of adenosine 37 of ANN-type tRNAs (tA) is a universal modification essential for translational accuracy and efficiency. The tA pathway uses two sequentially acting enzymes, YRDC and OSGEP, the latter being a subunit of the multiprotein KEOPS complex. We recently identified mutations in genes encoding four out of the five KEOPS subunits in children with Galloway-Mowat syndrome (GAMOS), a clinically heterogeneous autosomal recessive disease characterized by early-onset steroid-resistant nephrotic syndrome and microcephaly. Here we show that mutations in YRDC cause an extremely severe form of GAMOS whereas mutations in GON7, encoding the fifth KEOPS subunit, lead to a milder form of the disease. The crystal structure of the GON7/LAGE3/OSGEP subcomplex shows that the intrinsically disordered GON7 protein becomes partially structured upon binding to LAGE3. The structure and cellular characterization of GON7 suggest its involvement in the cellular stability and quaternary arrangement of the KEOPS complex.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722078 | PMC |
| http://dx.doi.org/10.1038/s41467-019-11951-x | DOI Listing |
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