The neck region of the myosin motor domain acts as a lever arm to generate movement.

Uyeda, Taro Q.P.; Abramson, Paul D.; Spudich, James A.

doi:10.1073/pnas.93.9.4459

Cited by 430 publications

(335 citation statements)

References 49 publications

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“…There was no distinction in life time of all binding events. Besides the lever arm [24], the converter domain was suggested to represent an alternative element of elastic distortion during force generation [25]. A FHC-related mutation within the converter domain substantially decreased myosin stiffness in fibers [26,27].…”

Section: Resultsmentioning

confidence: 99%

Molecular mechanism regulating myosin and cardiac functions by ELC

Lossie

Köhncke

Mahmoodzadeh

et al. 2014

Biochemical and Biophysical Research Communications

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The essential myosin light chain (ELC) is involved in modulation of force generation of myosin motors and cardiac contraction, while its mechanism of action remains elusive. We hypothesized that ELC could modulate myosin stiffness which subsequently determines its force production and cardiac contraction. We therefore generated heterologous transgenic mouse (TgM) strains with cardiomyocyte-specific expression of ELC with human ventricular ELC (hVLC-1; TgM hVLC-1 ) or E56G-mutated hVLC-1 (hVLC-1 E56G ; TgM E56G ). hVLC-1 or hVLC-1 E56G expression in TgM was around 39% and 41%, respectively of total VLC-1. Laser trap and in vitro motility assays showed that stiffness and actin sliding velocity of myosin with hVLC-1 prepared from TgM hVLC-1 (1.67pN/nm and 2.3µm/s, respectively) were significantly higher than myosin with hVLC-1 E56G prepared from TgM E56G (1.25pN/nm and 1.7µm/s, respectively) or myosin with mouse VLC-1 (mVLC-1) prepared from C57/BL6 (1.41 pN/nm and 1.5±0.03 µm/s , respectively). Maximal left ventricular pressure development of isolated perfused hearts in vitro prepared from TgM hVLC-1 (80.0mmHg) were significantly higher than hearts from TgM E56G (66.2mmHg) or C57/BL6 (59.3±3.9 mmHg). These findings show that ELCs decreased myosin stiffness, in vitro motility, and thereby cardiac functions in the order hVLC-1 > hVLC-1 E56G ≈ mVLC-1. They also suggest a molecular pathomechanism of cardiomyopathies caused by hVLC-1 mutations.

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Section: Resultsmentioning

confidence: 99%

Molecular mechanism regulating myosin and cardiac functions by ELC

Lossie

Köhncke

Mahmoodzadeh

et al. 2014

Biochemical and Biophysical Research Communications

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“…(53) The movement might represent a lever arm-like angle change of the coiled-coil stalk/ neck of Ncd, similar to the large rotation of the coiled-coil rod believed to occur in myosin. (55)(56)(57) A second displacement has been detected just before release of Ncd from the microtubule and has been postulated to be the large conformational change predicted to occur when ATP binds to the motor. (54) The structural basis of this movement has not yet been determined, although it may correspond to the rotation coupled to a translation of the relay helix, a4, detected in the kinesin motor KIF1A, which is thought to be triggered by binding of ATP to the motor.…”

Section: Minus-end Kinesin Motorsmentioning

confidence: 99%

Kinesin motors as molecular machines

Endow

2003

BioEssays

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SummaryMolecular motor proteins, fueled by energy from ATP hydrolysis, move along actin filaments or microtubules, performing work in the cell. The kinesin microtubule motors transport vesicles or organelles, assemble bipolar spindles or depolymerize microtubules, functioning in basic cellular processes. The mechanism by which motor proteins convert energy from ATP hydrolysis into work is likely to differ in basic ways from man-made machines. Several mechanical elements of the kinesin motors have now been tentatively identified, permitting researchers to begin to decipher the mechanism of motor function. The force-producing conformational changes of the motor and the means by which they are amplified are probably different for the plus-and minus-end kinesin motors.

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“…These and all following constructs were cloned into the expression vector pTIKL-Bsr-Exp. This vector is based on the extrachromasomal vector pTIKL (Uyeda et al, 1996), We replaced the G418 resistance gene of pTIKL with a blasticidin (Bsr) resistance gene (Sutoh, 1993). We also introduced an actinl5 promoter expression cassette for expression of the various rac constructs.…”

Section: Materials and Methods Mutant And Gfp Expression Constructsmentioning

confidence: 99%

Role of Dictyostelium racE in cytokinesis: mutational analysis and localization studies by use of green fluorescent protein.

Larochelle

Vithalani

Lozanne

1997

MBoC

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The small GTPase racE is essential for cytokinesis in Dictyostelium but its precise role in cell division is not known. To determine the molecular mechanism of racE function, we undertook a mutational analysis of racE. The exogenous expression of either wild-type racE or a constitutively active V20racE mutant effectively rescues the cytokinesis deficiency of racE null cells. In contrast, a constitutively inactive N25racE mutant fails to rescue the cytokinesis deficiency. Thus, cytokinesis requires only the activation of racE by GTP and not the inactivation of racE by hydrolysis of GTP. To determine the spatial distribution of racE, we created a fusion protein with GFP at the amino terminus of racE. Remarkably, GFP-racE fusion protein was fully competent to rescue the phenotype of racE null cells and, therefore, must reside in the same location as native racE. We found that GFP-racE localized to the plasma membrane of the cell throughout the entire cell cycle. Furthermore, constitutively active and inactive GFP-racE fusion proteins also localized to the plasma membrane. We mapped the domain required for plasma membrane localization to the carboxyl-terminal 40 amino acids of racE. This domain, however, is not sufficient to confer racE function onto a closely related GTPase. Taken together, these results suggest that racE functions at the cell cortex but it is not involved in determining the timing or placement of the contractile ring.

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The neck region of the myosin motor domain acts as a lever arm to generate movement.

Cited by 430 publications

References 49 publications

Molecular mechanism regulating myosin and cardiac functions by ELC

Molecular mechanism regulating myosin and cardiac functions by ELC

Kinesin motors as molecular machines

Role of Dictyostelium racE in cytokinesis: mutational analysis and localization studies by use of green fluorescent protein.

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