Related Experiment Video
Updated: May 14, 2026
08:59
4D Imaging of Protein Aggregation in Live Cells
Published on: April 5, 2013
Reduced native state stability in crowded cellular environment due to protein-protein interactions
Ryuhei Harada1, Naoya Tochio, Takanori Kigawa
1RIKEN Advanced Institute for Computational Science, 7-1-26 minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 Japan.
Journal of the American Chemical Society
|February 14, 2013
Summary
Cellular crowding can destabilize proteins through direct interactions, challenging the idea that it only favors compact structures. This study reveals protein-protein interactions as a key factor in protein stability under crowded conditions.
Area of Science:
- Molecular and Cellular Biology
- Biophysics
Background:
- Cellular crowding is crucial for protein structure and stability.
- The classical model emphasizes volume exclusion favoring compact native states.
Purpose of the Study:
- To investigate the impact of protein crowders on protein structure and stability.
- To explore the mechanisms beyond simple volume exclusion.
Main Methods:
- Molecular dynamics simulations
- Nuclear Magnetic Resonance (NMR) experiments
- Analysis of protein-protein interactions and energetics
Main Results:
- Protein crowders destabilize native protein states via direct protein-protein interactions.
- Crowding induces partial unfolding and conformational shifts, forming compact denatured states.
- NMR confirms structural changes due to crowding, differing from thermal or urea denaturation.
Conclusions:
- Protein-protein interactions are critical in crowding effects, influencing protein stability.
- Enthalpic and solvation contributions challenge the purely entropic view of crowding.
- Crowding can destabilize proteins, contrary to the classical volume exclusion model.
Related Concept Videos
01:53RNA Stability
Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
01:53RNA Stability
Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
01:28Protein Denaturation
The function of proteins depends on their native three-dimensional structure, which is dictated by the amino acid sequence of the specific protein. Folding of the polypeptide chain takes place under specific conditions that energetically favor the folded conformation. In contrast, protein denaturation occurs spontaneously under unfavorable conditions that disrupt the integrity of the folded conformation. Thus, the chemical and physical environment of a protein, such as significant changes in pH...
01:25Protein Folding
Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
01:22Protein Folding
Overview
01:45Destabilization of Microtubules
The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...