Abstract
As more and more recent investigations point out, force plays an important role in cellular regulation mechanisms. Biological responses to mechanical stress are often based on force-induced conformational changes of single molecules. The force sensor, titin kinase, is involved in a signaling complex that regulates protein turnover and transcriptional adaptation in striated muscle. The structural architecture of such a force sensor determines its response to force and must assure both activity and mechanical integrity, which are prerequisites for its function. Here, we use single-molecule force-clamp spectroscopy to show that titin kinase is organized in such a way that the regulatory domains have to unfold before secondary structure elements that determine the overall fold and catalytic function. The stepwise unfolding over many barriers with a topologically determined sequence assures that the protein can react to force by conformational changes while maintaining its structural integrity.
| Original language | English |
|---|---|
| Pages (from-to) | 1978-1986 |
| Number of pages | 9 |
| Journal | Biophysical Journal |
| Volume | 101 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 19 Oct 2011 |
Keywords
- Biocatalysis
- Biomechanical Phenomena
- Connectin
- Cytoskeleton
- Fibronectins
- Humans
- Markov Chains
- Mechanical Processes
- Microscopy, Atomic Force
- Models, Molecular
- Muscle Proteins
- Protein Kinases
- Protein Structure, Tertiary
- Protein Unfolding