Abstract
Molecular chaperones are commonly identified by their ability to suppress heat-induced protein aggregation. The muscle-specific molecular chaperone UNC-45B is known to be involved in myosin folding and is trafficked to the sarcomeres A-band during thermal stress. Here, we identify temperature-dependent structural changes in the UCS chaperone domain of UNC-45B that occur within a physiologically relevant heat-shock range. We show that distinct changes to the armadillo repeat protein topology result in exposure of hydrophobic patches, and increased flexibility of the molecule. These rearrangements suggest the existence of a novel thermosensor within the chaperone domain of UNC-45B. We propose that these changes may function to suppress aggregation under stress by allowing binding to a wide variety of aggregation prone loops on its client.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 123-130 |
| Number of pages | 8 |
| Journal | FEBS Letters |
| Volume | 589 |
| Issue number | 1 |
| DOIs | |
| State | Published - Feb 2 2015 |
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Keywords
- ANS fluorescence
- Circular-dichroism
- Molecular chaperone
- Structural transition
- Thermal stress
- UNC-45
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Cell Biology
- Genetics
- Molecular Biology
- Structural Biology
- Medicine(all)
Cite this
Thermally-induced structural changes in an armadillo repeat protein suggest a novel thermosensor mechanism in a molecular chaperone. / Bujalowski, Pawel; Nicholls, Paul; Barral, José M.; Oberhauser, Andres.
In: FEBS Letters, Vol. 589, No. 1, 02.02.2015, p. 123-130.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Thermally-induced structural changes in an armadillo repeat protein suggest a novel thermosensor mechanism in a molecular chaperone
AU - Bujalowski, Pawel
AU - Nicholls, Paul
AU - Barral, José M.
AU - Oberhauser, Andres
PY - 2015/2/2
Y1 - 2015/2/2
N2 - Molecular chaperones are commonly identified by their ability to suppress heat-induced protein aggregation. The muscle-specific molecular chaperone UNC-45B is known to be involved in myosin folding and is trafficked to the sarcomeres A-band during thermal stress. Here, we identify temperature-dependent structural changes in the UCS chaperone domain of UNC-45B that occur within a physiologically relevant heat-shock range. We show that distinct changes to the armadillo repeat protein topology result in exposure of hydrophobic patches, and increased flexibility of the molecule. These rearrangements suggest the existence of a novel thermosensor within the chaperone domain of UNC-45B. We propose that these changes may function to suppress aggregation under stress by allowing binding to a wide variety of aggregation prone loops on its client.
AB - Molecular chaperones are commonly identified by their ability to suppress heat-induced protein aggregation. The muscle-specific molecular chaperone UNC-45B is known to be involved in myosin folding and is trafficked to the sarcomeres A-band during thermal stress. Here, we identify temperature-dependent structural changes in the UCS chaperone domain of UNC-45B that occur within a physiologically relevant heat-shock range. We show that distinct changes to the armadillo repeat protein topology result in exposure of hydrophobic patches, and increased flexibility of the molecule. These rearrangements suggest the existence of a novel thermosensor within the chaperone domain of UNC-45B. We propose that these changes may function to suppress aggregation under stress by allowing binding to a wide variety of aggregation prone loops on its client.
KW - ANS fluorescence
KW - Circular-dichroism
KW - Molecular chaperone
KW - Structural transition
KW - Thermal stress
KW - UNC-45
UR - http://www.scopus.com/inward/record.url?scp=84918807786&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84918807786&partnerID=8YFLogxK
U2 - 10.1016/j.febslet.2014.11.034
DO - 10.1016/j.febslet.2014.11.034
M3 - Article
VL - 589
SP - 123
EP - 130
JO - FEBS Letters
JF - FEBS Letters
SN - 0014-5793
IS - 1
ER -