Abstract
The mutation Arg91Gly (R91G) in β-tropomyosin (β-TM) is known to cause distal arthrogryposis, a severe congenital disorder of muscle tissues. The influence of this mutation in β-TM on its structure and thermal denaturation was demonstrated. It was shown by the differential scanning calorimetry and circular dichroism that this point mutation dramatically decreased the thermal stability of the significant part of the β-TM (about a half of the molecule). This part of the β-TM molecule carrying R91G mutation unfolds at ∼28°C, i.e., at a much lower temperature than the other part of the molecule, which melts at ∼40°C. The data of the differential scanning calorimetry were compared with the results of temperature dependence of pyrene eximer fluorescence, which decreased upon the dissociation of two β-TM chains in the region of pyrene-labeled Cys-36. This comparison allowed one to conclude that this thermal transition reflected the thermal unfolding of the whole N-terminal part of β-TM. Interestingly, the destabilizing effect of Arg91Gly mutation spread for a rather long distance along the tropomyosin coiled-coil indicating a high cooperativity of the thermal denaturation within this part of β-TM.
Similar content being viewed by others
Abbreviations
- DSC:
-
differential scanning calorimetry
- CD:
-
circular dichroism
- β-TM:
-
β-tropomyosin
- R91G:
-
mutation Arg91Gly in β-TM
References
S. V. Perry, J. Muscle Res. Cell Motil. 22, 5 (2001).
S. S. Sung, A. E. Brassington, K. Grannatt, et al., Am. J. Hum. Genet. 72, 681 (2003).
E. Kremneva, S. Boussouf, O. Nikolaeva, et al. Biophys. J. 87, 3922 (2004).
M. Mirza, P. Robinson, E. Kremneva, et al. J. Biol. Chem. 282, 13487 (2007).
F. W. Studier, A. H. Rosenberg, J. J. Dunn, and J. W. Dubendorff, Methods Enzymol. 185, 60 (1990).
P. Robinson, L. Lipscomb, L. Preston, et al., FASEB J. 21, 896 (2007).
E. Kremneva, O. Nikolaeva, R. Maytum, et al., FEBS J. 273, 588 (2006).
Y. Ishii and S. S. Lehrer, Biochemistry 29, 1160 (1990).
M. M. Bradford, Anal. Biochem. 72, 248 (1976).
A. I. Dragan and P. L. Privalov, J. Mol. Biol. 343, 371 (2002).
P. W. Gunning, G. Schevzov, A. J. Kee, and E. C. Hardeman, Trends Cell Biol. 15, 333 (2005).
Author information
Authors and Affiliations
Corresponding author
Additional information
Original Russian Text © I.A. Nevzorov, C.S. Redwood, D.I. Levitsky, 2008, published in Biofizika, 2008, Vol. 53, No. 6, pp. 917–921.
Rights and permissions
About this article
Cite this article
Nevzorov, I.A., Redwood, C.S. & Levitsky, D.I. Effect of mutation Arg91Gly on the thermal stability of β-tropomyosin. BIOPHYSICS 53, 479–481 (2008). https://doi.org/10.1134/S0006350908060018
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S0006350908060018