Regulation of the ATPase activity of cross-linked actin-myosin subfragment 1 by troponin-tropomyosin

Biochemistry ◽  
1985 ◽  
Vol 24 (24) ◽  
pp. 7009-7014 ◽  
Author(s):  
Robert Thomas King ◽  
Lois E. Greene
Keyword(s):  
Atpase Activity ◽  
Myosin Subfragment ◽  
Myosin Subfragment 1

scholarly journals Molecular Mechanisms of Muscle Weakness Associated with E173A Mutation in Tpm3.12. Troponin Ca2+ Sensitivity Inhibitor W7 Can Reduce the Damaging Effect of This Mutation

2020 ◽  
Vol 21 (12) ◽  
pp. 4421
Author(s):  
Yurii S. Borovikov ◽  
Armen O. Simonyan ◽  
Stanislava V. Avrova ◽  
Vladimir V. Sirenko ◽  
Charles S. Redwood ◽  
...  
Keyword(s):  
Atpase Activity ◽  
Muscle Weakness ◽  
Conformational Changes ◽  
Molecular Mechanisms ◽  
Spatial Arrangement ◽  
Muscle Fibres ◽  
Thin Filaments ◽  
Myosin Subfragment ◽  
Myosin Subfragment 1

Substitution of Ala for Glu residue in position 173 of γ-tropomyosin (Tpm3.12) is associated with muscle weakness. Here we observe that this mutation increases myofilament Ca2+-sensitivity and inhibits in vitro actin-activated ATPase activity of myosin subfragment-1 at high Ca2+. In order to determine the critical conformational changes in myosin, actin and tropomyosin caused by the mutation, we used the technique of polarized fluorimetry. It was found that this mutation changes the spatial arrangement of actin monomers and myosin heads, and the position of the mutant tropomyosin on the thin filaments in muscle fibres at various mimicked stages of the ATPase cycle. At low Ca2+ the E173A mutant tropomyosin shifts towards the inner domains of actin at all stages of the cycle, and this is accompanied by an increase in the number of switched-on actin monomers and myosin heads strongly bound to F-actin even at relaxation. Contrarily, at high Ca2+ the amount of the strongly bound myosin heads slightly decreases. These changes in the balance of the strongly bound myosin heads in the ATPase cycle may underlie the occurrence of muscle weakness. W7, an inhibitor of troponin Ca2+-sensitivity, restores the increase in the number of myosin heads strongly bound to F-actin at high Ca2+ and stops their strong binding at relaxation, suggesting the possibility of using Ca2+-desensitizers to reduce the damaging effect of the E173A mutation on muscle fibre contractility.

Inhibition of Acto-Myosin Subfragment-1 ATPase Activity by Peptides Corresponding to Various Segments of the 20-kDa Domain of Myosin Heavy Chain1

1994 ◽  
Vol 115 (4) ◽  
pp. 701-707
Author(s):  
Masumi Eto ◽  
Katsuyoshi Isonishi ◽  
Yasuhiro Fukui ◽  
Fumi Morita ◽  
Norio Nishi ◽  
...  
Keyword(s):  
Atpase Activity ◽  
Myosin Subfragment ◽  
Myosin Subfragment 1
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