The myosin C-loop is an allosteric actin contact sensor in actomyosin

Katalin Ajtai, Miriam F. Halstead, Miklós Nyitrai, Alan R. Penheiter, Ye Zheng, Thomas P Burghardt

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Actin and myosin form the molecular motor in muscle. Myosin is the enzyme performing ATP hydrolysis under the allosteric control of actin such that actin binding initiates product release and force generation in the myosin power stroke. Non-equilibrium Monte Carlo molecular dynamics simulation of the power stroke suggested that a structured surface loop on myosin, the C-loop, is the actin contact sensor initiating actin activation of the myosin ATPase. Previous experimental work demonstrated C-loop binds actin and established the forward and reverse allosteric link between the C-loop and the myosin active site. Here, smooth muscle heavy meromyosin C-loop chimeras were constructed with skeletal (sCl) and cardiac (cCl) myosin C-loops substituted for the native sequence. In both cases, actin-activated ATPase inhibition is indicated mainly by the lower Vmax. In vitro motility was also inhibited in the chimeras. Motility data were collected as a function of myosin surface density, with unregulated actin, and with skeletal and cardiac isoforms of tropomyosin-bound actin for the wild type, cCl, and sCl. Slow and fast subpopulations of myosin velocities in the wild-type species were discovered and represent geometrically unfavorable and favorable actomyosin interactions, respectively. Unfavorable interactions are detected at all surface densities tested. Favorable interactions are more probable at higher myosin surface densities. Cardiac tropomyosin-bound actin promotes the favorable actomyosin interactions by lowering the inhibiting geometrical constraint barriers with a structural effect on actin. Neither higher surface density nor cardiac tropomyosin-bound actin can accelerate motility velocity in cCl or sCl, suggesting the element initiating maximal myosin activation by actin resides in the C-loop.

Original languageEnglish (US)
Pages (from-to)5263-5275
Number of pages13
JournalBiochemistry
Volume48
Issue number23
DOIs
StatePublished - Jun 16 2009

Fingerprint

Contact sensors
Actomyosin
Myosins
Actins
Tropomyosin
Muscle
Chemical activation
Stroke
Cardiac Myosins
Myosin Subfragments
Molecular Dynamics Simulation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Ajtai, K., Halstead, M. F., Nyitrai, M., Penheiter, A. R., Zheng, Y., & Burghardt, T. P. (2009). The myosin C-loop is an allosteric actin contact sensor in actomyosin. Biochemistry, 48(23), 5263-5275. https://doi.org/10.1021/bi900584q

The myosin C-loop is an allosteric actin contact sensor in actomyosin. / Ajtai, Katalin; Halstead, Miriam F.; Nyitrai, Miklós; Penheiter, Alan R.; Zheng, Ye; Burghardt, Thomas P.

In: Biochemistry, Vol. 48, No. 23, 16.06.2009, p. 5263-5275.

Research output: Contribution to journalArticle

Ajtai, K, Halstead, MF, Nyitrai, M, Penheiter, AR, Zheng, Y & Burghardt, TP 2009, 'The myosin C-loop is an allosteric actin contact sensor in actomyosin', Biochemistry, vol. 48, no. 23, pp. 5263-5275. https://doi.org/10.1021/bi900584q
Ajtai K, Halstead MF, Nyitrai M, Penheiter AR, Zheng Y, Burghardt TP. The myosin C-loop is an allosteric actin contact sensor in actomyosin. Biochemistry. 2009 Jun 16;48(23):5263-5275. https://doi.org/10.1021/bi900584q
Ajtai, Katalin ; Halstead, Miriam F. ; Nyitrai, Miklós ; Penheiter, Alan R. ; Zheng, Ye ; Burghardt, Thomas P. / The myosin C-loop is an allosteric actin contact sensor in actomyosin. In: Biochemistry. 2009 ; Vol. 48, No. 23. pp. 5263-5275.
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