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Paramagnetic Relaxation Enhancement for Detecting and Characterizing Self-Associations of Intrinsically Disordered Proteins
Published on: September 23, 2021
Structural characterization of the intrinsically disordered domain of Mycobacterium tuberculosis protein tyrosine
Anna Niesteruk1, Marie Hutchison1, Sridhar Sreeramulu1
1Goethe-University Frankfurt am Main, Institute for Organic Chemistry and Chemical Biology, Centre for Biomolecular Magnetic Resonance (BMRZ), Frankfurt am Main, Germany.
Abstract:
Although intrinsically disordered proteins or protein domains (IDPs or IDD) are less abundant in bacteria than in eukaryotes, their presence in pathogenic bacterial proteins is important for protein-protein interactions. The protein tyrosine kinase A (PtkA) from Mycobacterium tuberculosis possesses an 80-residue disordered region (IDDPtkA ) of unknown function, located N-terminally to the well-folded kinase core domain. Here, we characterize the conformation of IDDPtkA under varying biophysical conditions and phosphorylation using NMR-spectroscopy. Our results confirm that the N-terminal domain of PtkA exists as an IDD at physiological pH. Furthermore, phosphorylation of IDDPtkA increases the activity of PtkA. Our findings will complement future approaches in understanding molecular mechanisms of key proteins in pathogenic virulence.
Insights
Intrinsically disordered regions in bacterial proteins are key for interactions. Phosphorylation of the PtkA disordered region in Mycobacterium tuberculosis enhances kinase activity, impacting virulence.
Area of Science:
- Biochemistry
- Structural Biology
- Microbiology
Background:
- Intrinsically disordered proteins (IDPs) are less common in bacteria but crucial for protein interactions in pathogens.
- Mycobacterium tuberculosis protein tyrosine kinase A (PtkA) has an N-terminal intrinsically disordered domain (IDD_PtkA) of unknown function.
Discussion:
- NMR spectroscopy revealed IDD_PtkA maintains a disordered conformation at physiological pH.
- Phosphorylation of IDD_PtkA was observed to increase PtkA activity.
Key Insights:
- The N-terminal disordered region of PtkA is conformationally flexible.
- Post-translational modification (phosphorylation) modulates the activity of PtkA.
Outlook:
- Findings provide insights into the molecular mechanisms of pathogenic bacterial virulence factors.
- Further research can explore the role of IDPs in bacterial pathogenesis and drug target identification.
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