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Identification of an Intrinsically Disordered Region (IDR) in Arginyltransferase 1 (ATE1).
Misti Cartwright1, Rinky Parakra2, Ayomide Oduwole1
1Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, Baltimore, Maryland 21250, United States.
Mouse Arginyltransferase 1 (ATE1) has a complex structure with an intrinsically disordered region (IDR), unlike yeast ATE1. This IDR aids in ATE1-tRNAArg complex formation, offering new insights into arginylation.
Area of Science:
- Biochemistry and Molecular Biology
- Structural Biology
- Posttranslational Modifications
Background:
- Arginyltransferase 1 (ATE1) catalyzes arginylation, a crucial posttranslational modification (PTM) for cellular homeostasis.
- ATE1 dysfunction is linked to neurodegenerative disorders and cardiovascular issues in mammals.
- Previous studies primarily focused on yeast ATE1, leaving mammalian ATE1 mechanisms unclear.
Purpose of the Study:
- To structurally and biophysically characterize mouse (Mus musculus) ATE1.
- To elucidate the structural differences between mammalian and yeast ATE1.
- To investigate the role of intrinsically disordered regions (IDRs) in mammalian ATE1 function.
Main Methods:
- Size-exclusion chromatography (SEC)
- Small-angle X-ray scattering (SAXS)
- Hydrogen-deuterium exchange mass spectrometry (HDX-MS)
- AlphaFold modeling
- Bioinformatics analysis
Main Results:
- Mouse ATE1 exhibits greater structural complexity compared to yeast ATE1.
- An intrinsically disordered region (IDR) was identified in all mouse ATE1 splice variants, absent in yeast ATE1.
- Bioinformatic analysis revealed IDR-like sequences in mammalian ATE1 near the active site, facilitating ATE1-tRNAArg complex formation.
Conclusions:
- Mammalian ATE1 possesses a unique structural feature, an IDR, not found in yeast ATE1.
- The IDR plays a role in the interaction between ATE1 and tRNAArg, adding complexity to its function.
- These findings provide novel insights into the mechanism of arginylation in mammalian cells and suggest new avenues for research.
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