Introduction
Actin is one of the most abundant proteins, which can
assemble into many different structures in cells [2–4].
The biological activity of actin is regulated by
actin-binding proteins, which form a well-controlled
regulatory network. During their interactions these bio-
logical partners of actin affect its behaviour and
conformational properties. In vitro model systems were
often applied to elucidate the properties of actin fila-
ments. Previous studies involved the characterisation of
the effect of the polymerisation [5, 6], nucleotides [7, 8]
and the interaction of actin with myosin [9–13].
Phalloidin, isolated from Amanita phalloides
mushroom, and jasplakinolide from the marine sponge
Jaspis johnstoni, are actin-binding toxins, and used ex-
tensively for studying the conformational properties of
actin filaments. These drugs competitively bind to fila-
mentous actin with high affinity and causes the stabili-
zation of the filaments [14–16]. Differential scanning
calorimetry studies showed that phalloidin and
jasplakinolide are also able to stabilize actin filaments at
substochiometric concentration [17, 18].
It was in numerous cases that differential scan-
ning calorimetry (DSC) is an effective method to
study the thermal properties of actin [19–29]. In this
work we used DSC to study the complexes of
phalloidin and jasplakinolide with actin filaments
(F-actin). Apart from the analyses of the heat absorp-
tion vs. temperature curves we also took into account
the kinetic nature of the irreversible denaturation pro-
cesses. Using the model developed by Sanchez-Ruiz
et al. [1] we performed the detailed analysis of the
toxin-induced changes in the thermal stability of actin
filaments. This method allowed us to determine the
activation energies from the Arrhenius plots of the
first-order rate constant of denaturation for both
phalloidin and jasplakinolide stabilised actin fila-
ments. The results were in agreement with previous
observations that the stabilization of actin by these
drugs is different. The differences appear not only in
the extent of stabilization, but also in the kinetic prop-
erties of the toxin modified processes.
Materials and methods
Materials
KCl, MgCl
2
, CaCl
2
, EGTA, Tris and phalloidin were
obtained from Sigma Chem Co. (St. Louis, MO,
USA). Jasplakinolide was purchased from Molecular
Probes (Eugene, OR, USA). ATP and
2-mercaptoethanol were obtained from Merk
(Darmstadt, Germany). NaN
3
was purchased from
Fluka (Switzerland).
Protein preparation
Aceton-dried powder from rabbit skeletal muscle was
obtained as described previously [30]. Actin was pre-
pared according to the method of Spudich and Watt
[31] and stored in 2 mM Tris-HCl (pH 8.0), 0.2 mM
ATP, 0.1 mM CaCl
2
, 0.5 mM MEA (buffer A). Before
the measurements the actin monomer solution was
clarified by ultracentrifugation at 100.000 g, 2 h, 4°C.
The concentration of G-actin was determined spectro-
1388–6150/$20.00 Akadémiai Kiadó, Budapest, Hungary
© 2005 Akadémiai Kiadó, Budapest Springer, Dordrecht, The Netherlands
Journal of Thermal Analysis and Calorimetry, Vol. 82 (2005) 275–279
THE EFFECT OF TOXINS ON THE THERMAL STABILITY OF ACTIN
FILAMENTS BY DIFFERENTIAL SCANNING CALORIMETRY
Beáta Bugyi
1
, G. Papp
1
, Sz. Halasi
1
and B. Visegrády
2*
1
Department of Biophysics, Faculty of Medicine, University of Pécs, Pécs, Szigeti str. 12, 7624, Hungary
2
Research Group for Fluorescence Spectroscopy, Office for Academy Research Groups Attached to Universities and Other
Institutions at the Department of Biophysics, Faculty of Medicine, University of Pécs, Pécs, Szigeti str. 12, 7624, Hungary
In our present study we performed the detailed characterisation of jasplakinolide and phalloidin on the thermal stability of actin fila-
ments. The heat absorption curves were analysed by using the model established by Sanchez-Ruiz et al. [1]. The analysis provided
the activation energies attributed to the heat denaturation of actin filaments in the absence and in the presence of toxins. The results
indicated that there are kinetic differences between the toxin-mediated stabilization of the Ca
2+
-and Mg
2+
-actin filaments. The effect
of toxins appeared to be cation dependent.
Keywords: actin, cation, differential scanning calorimetry, jasplakinolide, phalloidin, protein conformation and dynamics
* Author for correspondence: balazs.visegrady@aok.pte.hu