Nucleotide binding induces global and local structural changes of myosin head in muscle fibres

Lőrinczy, D.; Belágyi, Joseph

doi:10.1046/j.0014-2956.2001.02548.x

Cited by 22 publications

(6 citation statements)

References 44 publications

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“…3). Similar approach had been successfully applied previously for the analysis of complex heat absorption curves [34]. The Gaussian fit resolved the T m values of 54.3 ± 0.5 °C and 60.0 ± 2.1 °C, which were close to those obtained without the decomposition.…”

Section: Dsc Results On Adp-actin Filamentssupporting

confidence: 48%

Nucleotide dependent differences between the α-skeletal and α-cardiac actin isoforms

Orbán

Lőrinczy²,

Nyitrai³

et al. 2008

Biochemical and Biophysical Research Communications

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The thermodynamic properties of the actin filaments prepared from cardiomyocytes were investigated with differential scanning calorimetry. This method could distinguish between the α-cardiac and α-skeletal components of the actin filaments polymerised from ADP-actin monomers by their different melting temperatures (T m ). Similar separation was not possible with filaments polymerised from ATP-actin monomers. Further analyses revealed that the activation energy (E act ) was greater for filaments of α-skeletal actin than for α-cardiac actin monomers when the filaments were polymerised from ADP-actin monomers. These results showed that the α-cardiac actin filaments were thermodynamically less stable than the filaments of α-skeletal actin and their difference was nucleotide dependent. Based on these results and considering previous observations it was concluded that the existence of two actin isoforms and their nucleotide dependent conformational differences are part of the tuning regulatory mechanism by which the cardiac muscle cells can maintain their biological function under pathological conditions. KeywordsCalorimetry; Thermodynamics; Stability; Nucleotides; Actin filament; Protein conformation Actin is an important intracellular protein with versatile cellular functions [1][2][3][4]. In the heart muscle cells both α-cardiac and α-skeletal isoforms of actin can be found [5,6]. The contribution of the skeletal actin isoform in the cardiac muscle is 16-24% of the total actin [5,6]. The actin binds an ATP in complex with a divalent magnesium ion under physiological circumstances [7]. The ATP is hydrolysed during the polymerisation of the actin monomers and the filaments contain mainly ADP in their matured form [8]. The role of the nucleotide in the mechano-chemical properties of the actin filament was emphasized by Janmey and colleagues when they suggested that the energy utilized during the breakdown of the ATP could be stored in the protein [9]. The characterisation of the ADPactin revealed a change in the subdomain structure and the dynamics of the protein as well [10,11]. Increased inter-monomer flexibility and decreased stiffness were observed when the actin filaments were polymerised from ADP-actin monomers [9,12].The work of some actin-binding proteins (e.g. thymosin β4, ARP 2/3 and cofilin) in the cardiac muscle tissue is strongly influenced by the quality of the actin-bound nucleotide [13][14][15]. Based on the essential roles of the actin-binding proteins in the eukaryotic cells a detailed investigation of the different forms of their targeted actin isoforms is essential to understand the complex work of the cytoskeletal network. In the non-muscle cells the ATP Differential scanning calorimetry (DSC) is able to determine directly the global thermodynamic properties of a protein and reveal differences on the sub-molecular level as well [20]. In this work the thermodynamic features of actin filaments polymerised from ADP containing actin monomers of heart muscle cells were characterised with the me...

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Section: Dsc Results On Adp-actin Filamentssupporting

confidence: 48%

Nucleotide dependent differences between the α-skeletal and α-cardiac actin isoforms

Orbán

Lőrinczy²,

Nyitrai³

et al. 2008

Biochemical and Biophysical Research Communications

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“…We could prove their similar effect in myofibrils, which are a real muscle model [27,28]. We have performed our measurements on muscle fibres too, and achieved similar temperature shift for all intermediate states of ATP hydrolysis in the higher temperature range [29][30][31][32][33][34][35][36][37][38][39].…”

Section: Discussionmentioning

confidence: 80%

Cyclophosphamide treatment evoked side effects on skeletal muscle monitored by DSC

Lőrinczy

2020

J Therm Anal Calorim

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Polyneuropathy is defined as a simultaneous malfunction of several peripheral nerves, which could be a side effect of cancer therapy as well. Many kinds of drugs, supposedly cyclophosphamide, also can induce a disease classified as toxic polyneuropathy. It is well known that a severe problem in the locomotor activity can join to it. Recently, we have no enough information about the attacked points in the structure of muscle proteins, as well as about the change in the interaction of myosin actin. In the present study, we analyse this side effect on skeletal muscle (m. gastrocnemius) by differential scanning calorimetry (DSC), as an established thermal analysis method, to follow the possible consequence of drug treatment in the most important muscle protein. We used cyclophosphamide-treated in vitro animal model (guinea pig) with a comparable dosage and time handling of human protocol to show evidences of this drug-induced effects. According to our results, we could show a dose-dependent difference between thermal parameters (denaturation temperature and calorimetric enthalpy) of untreated and treated samples assigned to their contractile proteins (actin and myosin), which can be detected by DSC. It proved that we can create new possibilities in the detection and prognosis of expected and unwanted side effects of cyclophosphamide, such as change of locomotor activity joined to polyneuropathy.

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“…The structure formation alters the dynamic and energetic properties of the contractile proteins, the consequence of that is the shift of the melting points measured in solution on intact myosin from rabbit psoas muscle to higher temperatures in rigor [28]. This increase of transition temperatures is evidence that particular regions of myosin and actin are subjected to stabilizing forces in the filament system leading to alteration of the transition temperatures.…”

Section: Resultsmentioning

confidence: 99%

Differential scanning calorimetry study of glycerinated rabbit psoas muscle fibres in intermediate state of ATP hydrolysis

et al. 2007

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Background: Thermal denaturation experiments were extended to study the thermal behaviour of the main motor proteins (actin and myosin) in their native environment in striated muscle fibres. The interaction of actin with myosin in the highly organized muscle structure is affected by internal forces; therefore their altered conformation and interaction may differ from those obtained in solution. The energetics of long functioning intermediate states of ATP hydrolysis cycle was studied in muscle fibres by differential scanning calorimetry (DSC).

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Nucleotide binding induces global and local structural changes of myosin head in muscle fibres

Cited by 22 publications

References 44 publications

Nucleotide dependent differences between the α-skeletal and α-cardiac actin isoforms

Nucleotide dependent differences between the α-skeletal and α-cardiac actin isoforms

Cyclophosphamide treatment evoked side effects on skeletal muscle monitored by DSC

Differential scanning calorimetry study of glycerinated rabbit psoas muscle fibres in intermediate state of ATP hydrolysis

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