TY - JOUR
T1 - Investigation on different chemical stability of mitochondrial Hsp60 and its precursor
AU - Ricci, Caterina
AU - Carrotta, Rita
AU - Rappa, Giacoma Cinzia
AU - Mangione, Maria Rosalia
AU - Librizzi, Fabio
AU - San Biagio, Pier Luigi
AU - Amenitsch, Heinz
AU - Ortore, Maria Grazia
AU - Vilasi, Silvia
PY - 2017/10/1
Y1 - 2017/10/1
N2 - In the large class of molecules that maintain protein homeostasis, called molecular chaperones, chaperonins constitute a subclass that specifically assist the correct folding of newly synthesized proteins. Among them, Hsp60 is composed of a double heptameric ring structure with a large central cavity where the unfolded protein binds via hydrophobic interactions and is supported, in this function, by the co-chaperonin Hsp10. Hsp60 is typically located in the mitochondria, but in some pathological situations, such as cancers and chronic inflammatory diseases, Hsp60 accumulates in the cytoplasm. In these cases, cytoplasmatic Hsp60 is a mixture of mitochondrial Hsp60 secreted from mitochondria upon stress, and its precursor, called naïve Hsp60, never entered into the organella. The difference between the naïve and mitochondrial Hsp60s resides in the absence of the mitochondrial import signal (MIS) in the mitochondrial form, but information on their different structure and stability is still lacking. We present here a study on the stability against a chemical denaturant, of the different cytoplasmic Hsp60 species. By combining Circular Dichroism and Small Angle X-ray Scattering as experimental biophysical techniques to investigate Hsp60, we find that naïve and mitochondrial Hsp60 (mtHsp60) forms differ in their stability. Furthermore, specific responses from the two forms are discussed in terms of the biological environment they are working in, thus opening new questions on their biological function.
AB - In the large class of molecules that maintain protein homeostasis, called molecular chaperones, chaperonins constitute a subclass that specifically assist the correct folding of newly synthesized proteins. Among them, Hsp60 is composed of a double heptameric ring structure with a large central cavity where the unfolded protein binds via hydrophobic interactions and is supported, in this function, by the co-chaperonin Hsp10. Hsp60 is typically located in the mitochondria, but in some pathological situations, such as cancers and chronic inflammatory diseases, Hsp60 accumulates in the cytoplasm. In these cases, cytoplasmatic Hsp60 is a mixture of mitochondrial Hsp60 secreted from mitochondria upon stress, and its precursor, called naïve Hsp60, never entered into the organella. The difference between the naïve and mitochondrial Hsp60s resides in the absence of the mitochondrial import signal (MIS) in the mitochondrial form, but information on their different structure and stability is still lacking. We present here a study on the stability against a chemical denaturant, of the different cytoplasmic Hsp60 species. By combining Circular Dichroism and Small Angle X-ray Scattering as experimental biophysical techniques to investigate Hsp60, we find that naïve and mitochondrial Hsp60 (mtHsp60) forms differ in their stability. Furthermore, specific responses from the two forms are discussed in terms of the biological environment they are working in, thus opening new questions on their biological function.
KW - CD
KW - Guanidinium chloride
KW - Hsp60
KW - SAXS
KW - Stability-function relationship
KW - Unfolding
UR - http://www.scopus.com/inward/record.url?scp=85026376970&partnerID=8YFLogxK
U2 - 10.1016/j.bpc.2017.07.008
DO - 10.1016/j.bpc.2017.07.008
M3 - Article
C2 - 28774748
AN - SCOPUS:85026376970
VL - 229
SP - 31
EP - 38
JO - Biophysical Chemistry
JF - Biophysical Chemistry
SN - 0301-4622
ER -