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Updated: Jul 17, 2025
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Assaying for Inorganic Polyphosphate in Bacteria
Published on: January 21, 2019
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Modification of histidine repeat proteins by inorganic polyphosphate.
Nolan Neville1, Kirsten Lehotsky1, Zhiyun Yang1
1Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON K7L 3N6, Canada.
Cell Reports
|September 3, 2023
Summary
Inorganic polyphosphate (polyP) modifies histidine-rich proteins through a non-covalent histidine polyphosphate modification (HPM). This modification impacts protein function and phase separation, revealing a novel regulatory mechanism.
Area of Science:
- Biochemistry
- Molecular Biology
- Post-Translational Modifications
Background:
- Inorganic polyphosphate (polyP) is ubiquitous in organisms.
- PolyP is known to modify lysine residues via non-enzymatic post-translational modification (PTM).
Purpose of the Study:
- To investigate novel mechanisms of polyP modification in proteins.
- To identify proteins and characterize the nature of polyP modification on histidine residues.
Main Methods:
- Screening of human and yeast proteomes for histidine repeat proteins.
- Analysis of polyP modification using NuPAGE gels.
- Assessing the impact of histidine polyphosphate modification (HPM) on protein kinase and transcription factor activity.
Main Results:
- Identified 30 human and yeast proteins undergoing histidine polyphosphate modification (HPM).
- Demonstrated that HPM is histidine-dependent and non-covalent, yet stable under denaturing conditions.
- Showed HPM disrupts phase separation and kinase activity of DYRK1A, and inhibits MafB activity.
Conclusions:
- Histidine polyphosphate modification (HPM) is a novel, non-covalent PTM.
- HPM acts as a regulatory mechanism affecting protein function, including phase separation and enzymatic activity.
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