Nickel and GTP Modulate Helicobacter pylori UreG Structural Flexibility
Annalisa Pierro1, Emilien Etienne1, Guillaume Gerbaud1
1Aix Marseille Univ, CNRS, BIP, Bioénergétique et Ingénierie des Protéines, IMM, Marseille, France.
Biomolecules
|July 26, 2020
Summary
UreG, a GTPase essential for urease enzyme maturation, exhibits flexible behavior in solution. Combined metal and nucleotide binding induces a structural change, revealing protein dynamics crucial for nickel delivery.
Area of Science:
- Biochemistry
- Structural Biology
- Enzymology
Background:
- UreG is a P-loop GTP hydrolase crucial for nickel-containing urease maturation.
- Urease is essential across diverse organisms including plants, fungi, bacteria, and archaea.
- UreG facilitates Ni(II) delivery to apo-urease within a multi-protein complex.
Purpose of the Study:
- To investigate the solution structural dynamics of Helicobacter pylori UreG.
- To determine the effects of Ni(II) and GTP on UreG protein mobility.
- To understand the interplay between UreG, Ni(II), and GTP in enzyme activation.
Main Methods:
- Isothermal titration calorimetry (ITC).
- Site-directed spin labeling (SDSL) coupled with electron paramagnetic resonance (EPR) spectroscopy.
- Investigated protein dynamics in solution.
Main Results:
- Helicobacter pylori UreG displays intrinsically disordered and flexible behavior in solution.
- Crystallographic structures may not fully represent solution dynamics.
- Ni(II) and GTP binding individually maintain protein flexibility.
- Concomitant addition of Ni(II) and GTP induces a specific structural change via inter-region crosstalk.
Conclusions:
- UreG's flexible nature is key to its function in urease maturation.
- The study reveals novel insights into UreG's dynamic response to metal and nucleotide binding.
- Understanding these dynamics is vital for elucidating urease activation mechanisms.
Keywords:
EPR spectroscopyintrinsically disordered proteinsisothermal titration calorimetryprotein structural dynamicsprotein-ligand interactionsite-directed spin labelingMore Related Videos
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