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Single-Molecule Tracking Microscopy - A Tool for Determining the Diffusive States of Cytosolic Molecules
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Single-trajectory Bayesian modeling reveals multi-state diffusion of the MSH sliding clamp
Seongyu Park1,2, Inho Yang1, Jinseob Lee3
1Department of Physics, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
NPJ Systems Biology and Applications
|April 29, 2026
Summary
DNA mismatch repair (MMR) protein MutS homologs (MSH) exhibit complex diffusion dynamics. ATP-bound MSH forms a sliding clamp with three distinct states, challenging previous models of simple Brownian motion.
Area of Science:
- Molecular Biology
- Genomics
- Biophysics
Background:
- DNA mismatch repair (MMR) is vital for genomic integrity.
- MutS homologs (MSH) detect DNA mismatches and recruit MMR proteins.
- MSH has different functions and diffusion dynamics when bound to ADP versus ATP.
Purpose of the Study:
- To investigate the diffusion dynamics of the ATP-bound MSH sliding clamp.
- To challenge the conventional view of simple Brownian motion for the ATP-bound clamp.
- To quantitatively model MSH clamp diffusion.
Main Methods:
- Single-particle tracking experiments.
- Bayesian diffusion-state analysis framework.
- Quantitative modeling of diffusion characteristics.
Main Results:
- Diffusion characteristics do not fit a single-state model.
- Three discrete diffusion states (D1, D2, D3) were identified.
- Transitions between states occur primarily through an intermediate D2 state.
Conclusions:
- ATP-bound MSH clamp diffusion is not simple Brownian motion.
- Multi-state dynamics suggest conformational switching in the MSH clamp.
- MSH clamp diffusion is more intricate and regulated than previously understood.
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