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Updated: Feb 14, 2026

Detection of Small GTPase Prenylation and GTP Binding Using Membrane Fractionation and GTPase-linked Immunosorbent Assay
Published on: November 11, 2018
Induced opening of conformational switch I in GTP-bound Ran GTPase
Janka Czigleczki1, Balint Dudas2, Erika Balog1
1Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary.
Ran GTPase regulates cell transport by switching between active and inactive states. This study reveals a new mechanism where disrupting key interactions forces the active RanGTP into an inactive state, offering therapeutic insights.
Area of Science:
- Molecular Biology
- Structural Biology
- Biochemistry
Background:
- Ran is a small GTPase crucial for nucleocytoplasmic transport.
- It cycles between GDP-bound (inactive) and GTP-bound (active) states.
- Conformational changes in switch I and II regions regulate its activity.
Purpose of the Study:
- To describe an induced conformational change in RanGTP.
- To identify the structural mechanism driving this inactivation.
- To explore potential therapeutic targets.
Main Methods:
- Structural analysis of RanGTP.
- Investigating conformational changes upon disruption of specific interactions.
Main Results:
- RanGTP undergoes an induced conformational change, opening switch I to an inactive state.
- Disruption of Thr42-Mg2+ coordination and the Phe35-GTP-Lys152 triad triggers this.
- Lys152 is identified as critical for stabilizing the active Ran conformation.
Conclusions:
- A novel mechanism for RanGTP inactivation is described.
- Disruption of key interactions leads to full switch I opening.
- Findings may inform therapeutic strategies for cancers with dysregulated Ran.
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