Journal of Muscle Research and Cell Motility

, Volume 29, Issue 6–8, pp 173–176 | Cite as

Stability of two β-tropomyosin isoforms: effects of mutation Arg91Gly

  • Ilya Nevzorov
  • Charles Redwood
  • Dmitrii Levitsky


In order to comprehend the domain structure of two β-tropomyosin (β-Tm) isoforms (skeletal muscle and smooth muscle β-Tm) and the influence of the disease-causing mutation Arg91Gly on it, we studied the thermal unfolding of these tropomyosin species by means of differential scanning calorimetry (DSC). Our results show that the studied point mutation dramatically decreases thermal stability of a significant part of both β-Tm isoforms (about a half of the molecule) that unfolds as a cooperative unit (calorimetric domain). We have assigned this domain to the N-terminal part of the molecule combining, in the case of smooth muscle β-Tm, DSC studies with measurements of temperature dependence of pyrene excimer fluorescence, whose decrease reflects dissociation of two β-Tm chains in the region of pyrene-labeled Cys-36. Interestingly, the destabilizing effect of the mutation spreads along the coiled-coil reflecting the high extent of cooperativity within this part of the β-Tm molecule.


β-tropomyosin Thermal unfolding Protein stability Differential scanning calorimetry 



This work was supported in part by the Russian Foundation for Basic Research (grant 09-04-00339).


  1. Kremneva E, Boussouf S, Nikolaeva O, Maytum R, Geeves MA, Levitsky DI (2004) Effects of two familial hypertrophic cardiomyopathy mutations in α-tropomyosin, Asp175Asn and Glu180Gly, on the thermal unfolding of actin-bound tropomyosin. Biophys J 87:3922–3933. doi: 10.1529/biophysj.104.048793 PubMedCrossRefGoogle Scholar
  2. Perry SV (2001) Vertebrate tropomyosin: distribution, properties and function. J Muscle Res Cell Motil 22:5–49. doi: 10.1023/A:1010303732441 PubMedCrossRefGoogle Scholar
  3. Robinson P, Lipscomb S, Preston L, Altin E, Watkins H, Ashley C, Redwood C (2007) Mutations in fast skeletal troponin I, troponin T, and β-tropomyosin that cause distal arthrogryposis all increase contractile function. FASEB J 21:896–905. doi: 10.1096/fj.06-6899com PubMedCrossRefGoogle Scholar
  4. Sumida JP, Wu E, Lehrer SS (2008) Conserved Asp-137 imparts flexibility to tropomyosin and affects function. J Biol Chem 14:6728–6734. doi: 10.1074/jbc.M707485200 CrossRefGoogle Scholar
  5. Sung SS, Brassington AM, Grannatt K, Rutherford A, Whitby FG, Krakowiak PA, Jorde LB, Carey JC, Bamshad M (2003) Mutations in genes encoding fast-twitch contractile proteins cause distal arthrogryposis syndromes. Am J Hum Genet 72:681–690. doi: 10.1086/368294 PubMedCrossRefGoogle Scholar
  6. Ueno H (1984) Local structural changes in tropomyosin detected by a trypsin probe method. Biochemistry 23:4791–4798. doi: 10.1021/bi00315a040 PubMedCrossRefGoogle Scholar
  7. Williams DLJ, Swenson CA (1981) Tropomyosin stability: assignment of thermally induced conformational transitions to separate regions of the molecule. Biochemistry 20:3856–3864. doi: 10.1021/bi00516a029 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Ilya Nevzorov
    • 1
    • 2
  • Charles Redwood
    • 3
  • Dmitrii Levitsky
    • 1
  1. 1.A.N. Bach Institute of BiochemistryRussian Academy of SciencesMoscowRussia
  2. 2.Department of BiochemistryMoscow State UniversityMoscowRussia
  3. 3.Department of Cardiovascular MedicineUniversity of OxfordOxfordUK

Personalised recommendations