On the thermal and chemical stability of DNAJB6b and its globular domains
(2025) In Biophysical Chemistry 320-321.- Abstract
The chaperone DNAJB6b (JB6) plays important roles in increasing amyloid protein solubility and inhibiting amyloid fibril formation, a causative factor for neurodegenerative diseases like Alzheimer's and Parkinson's disease. Insights into the biophysical properties of JB6, including its structure, self-assembly and stability towards denaturation, may enhance the understanding of the physicochemical basis of chaperone action. However, many of the biophysical properties of the chaperone remain elusive. Here, we investigated the structure and stability of JB6 and its domains towards thermal and chemical denaturation using Fourier transform infrared and circular dichroism spectroscopy to examine the thermodynamic properties. Both domains act... (More)
The chaperone DNAJB6b (JB6) plays important roles in increasing amyloid protein solubility and inhibiting amyloid fibril formation, a causative factor for neurodegenerative diseases like Alzheimer's and Parkinson's disease. Insights into the biophysical properties of JB6, including its structure, self-assembly and stability towards denaturation, may enhance the understanding of the physicochemical basis of chaperone action. However, many of the biophysical properties of the chaperone remain elusive. Here, we investigated the structure and stability of JB6 and its domains towards thermal and chemical denaturation using Fourier transform infrared and circular dichroism spectroscopy to examine the thermodynamic properties. Both domains act as independent folding units. We find that the N-terminal domain (NTD) of JB6 is more stable than its C-terminal domain (CTD). Both domains are stabilized in the context of the full-length protein. The intact protein unfolds in a step-wise manner when subjected to a denaturing agent with the CTD unfolding at a lower denaturant concentration than the NTD. The combination of thermal and chemical denaturation followed by differential scanning fluorimetry revealed the enthalpy changes (22.6 and 26.4 kJ mol−1) and heat capacity changes (2.8 and 3.0 kJ/(mol*K)) upon denaturation of NTD alone and of NTD within the full-length protein, respectively. The understanding of JB6's biophysical properties complements the increasing amount of data on JB6's interactions with client proteins, paving the way for further investigation of the mechanism of its cellular function.
(Less)
- author
- Fricke, Celia LU ; Milošević, Jelica LU ; Carlsson, Andreas LU ; Boyens-Thiele, Lars ; Dubackic, Marija LU ; Olsson, Ulf LU ; Buell, Alexander K. and Linse, Sara LU
- organization
- publishing date
- 2025-05
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Chaperone, Folding, Reconstitution, Stability, Unfolding
- in
- Biophysical Chemistry
- volume
- 320-321
- article number
- 107401
- publisher
- Elsevier
- external identifiers
-
- scopus:85217207789
- pmid:39938325
- ISSN
- 0301-4622
- DOI
- 10.1016/j.bpc.2025.107401
- language
- English
- LU publication?
- yes
- id
- 96e2e604-8c52-4931-b8d7-858bbdb213d7
- date added to LUP
- 2025-03-24 09:35:02
- date last changed
- 2025-07-14 16:12:18
@article{96e2e604-8c52-4931-b8d7-858bbdb213d7, abstract = {{<p>The chaperone DNAJB6b (JB6) plays important roles in increasing amyloid protein solubility and inhibiting amyloid fibril formation, a causative factor for neurodegenerative diseases like Alzheimer's and Parkinson's disease. Insights into the biophysical properties of JB6, including its structure, self-assembly and stability towards denaturation, may enhance the understanding of the physicochemical basis of chaperone action. However, many of the biophysical properties of the chaperone remain elusive. Here, we investigated the structure and stability of JB6 and its domains towards thermal and chemical denaturation using Fourier transform infrared and circular dichroism spectroscopy to examine the thermodynamic properties. Both domains act as independent folding units. We find that the N-terminal domain (NTD) of JB6 is more stable than its C-terminal domain (CTD). Both domains are stabilized in the context of the full-length protein. The intact protein unfolds in a step-wise manner when subjected to a denaturing agent with the CTD unfolding at a lower denaturant concentration than the NTD. The combination of thermal and chemical denaturation followed by differential scanning fluorimetry revealed the enthalpy changes (22.6 and 26.4 kJ mol<sup>−1</sup>) and heat capacity changes (2.8 and 3.0 kJ/(mol*K)) upon denaturation of NTD alone and of NTD within the full-length protein, respectively. The understanding of JB6's biophysical properties complements the increasing amount of data on JB6's interactions with client proteins, paving the way for further investigation of the mechanism of its cellular function.</p>}}, author = {{Fricke, Celia and Milošević, Jelica and Carlsson, Andreas and Boyens-Thiele, Lars and Dubackic, Marija and Olsson, Ulf and Buell, Alexander K. and Linse, Sara}}, issn = {{0301-4622}}, keywords = {{Chaperone; Folding; Reconstitution; Stability; Unfolding}}, language = {{eng}}, publisher = {{Elsevier}}, series = {{Biophysical Chemistry}}, title = {{On the thermal and chemical stability of DNAJB6b and its globular domains}}, url = {{http://dx.doi.org/10.1016/j.bpc.2025.107401}}, doi = {{10.1016/j.bpc.2025.107401}}, volume = {{320-321}}, year = {{2025}}, }