18.7: Allosteric Change and the Microcontraction Cycle Resolves the Contraction Paradox
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- 89025
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\(\newcommand{\avec}{\mathbf a}\) \(\newcommand{\bvec}{\mathbf b}\) \(\newcommand{\cvec}{\mathbf c}\) \(\newcommand{\dvec}{\mathbf d}\) \(\newcommand{\dtil}{\widetilde{\mathbf d}}\) \(\newcommand{\evec}{\mathbf e}\) \(\newcommand{\fvec}{\mathbf f}\) \(\newcommand{\nvec}{\mathbf n}\) \(\newcommand{\pvec}{\mathbf p}\) \(\newcommand{\qvec}{\mathbf q}\) \(\newcommand{\svec}{\mathbf s}\) \(\newcommand{\tvec}{\mathbf t}\) \(\newcommand{\uvec}{\mathbf u}\) \(\newcommand{\vvec}{\mathbf v}\) \(\newcommand{\wvec}{\mathbf w}\) \(\newcommand{\xvec}{\mathbf x}\) \(\newcommand{\yvec}{\mathbf y}\) \(\newcommand{\zvec}{\mathbf z}\) \(\newcommand{\rvec}{\mathbf r}\) \(\newcommand{\mvec}{\mathbf m}\) \(\newcommand{\zerovec}{\mathbf 0}\) \(\newcommand{\onevec}{\mathbf 1}\) \(\newcommand{\real}{\mathbb R}\) \(\newcommand{\twovec}[2]{\left[\begin{array}{r}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\ctwovec}[2]{\left[\begin{array}{c}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\threevec}[3]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\cthreevec}[3]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\fourvec}[4]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\cfourvec}[4]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\fivevec}[5]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\cfivevec}[5]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\mattwo}[4]{\left[\begin{array}{rr}#1 \amp #2 \\ #3 \amp #4 \\ \end{array}\right]}\) \(\newcommand{\laspan}[1]{\text{Span}\{#1\}}\) \(\newcommand{\bcal}{\cal B}\) \(\newcommand{\ccal}{\cal C}\) \(\newcommand{\scal}{\cal S}\) \(\newcommand{\wcal}{\cal W}\) \(\newcommand{\ecal}{\cal E}\) \(\newcommand{\coords}[2]{\left\{#1\right\}_{#2}}\) \(\newcommand{\gray}[1]{\color{gray}{#1}}\) \(\newcommand{\lgray}[1]{\color{lightgray}{#1}}\) \(\newcommand{\rank}{\operatorname{rank}}\) \(\newcommand{\row}{\text{Row}}\) \(\newcommand{\col}{\text{Col}}\) \(\renewcommand{\row}{\text{Row}}\) \(\newcommand{\nul}{\text{Nul}}\) \(\newcommand{\var}{\text{Var}}\) \(\newcommand{\corr}{\text{corr}}\) \(\newcommand{\len}[1]{\left|#1\right|}\) \(\newcommand{\bbar}{\overline{\bvec}}\) \(\newcommand{\bhat}{\widehat{\bvec}}\) \(\newcommand{\bperp}{\bvec^\perp}\) \(\newcommand{\xhat}{\widehat{\xvec}}\) \(\newcommand{\vhat}{\widehat{\vvec}}\) \(\newcommand{\uhat}{\widehat{\uvec}}\) \(\newcommand{\what}{\widehat{\wvec}}\) \(\newcommand{\Sighat}{\widehat{\Sigma}}\) \(\newcommand{\lt}{<}\) \(\newcommand{\gt}{>}\) \(\newcommand{\amp}{&}\) \(\definecolor{fillinmathshade}{gray}{0.9}\)Whereas dynein and kinesin are motor proteins that “walk” along microtubules, myosins are motor proteins that walk along microfilaments. All these motor proteins are ATPases that use the free energy of ATP hydrolysis to effect conformational changes that result in the walking (i.e., motility). In skeletal muscle, allosteric changes in myosin heads enable the myosin rods to do the walking along the sarcomere thin (F-actin) filaments. When placed in sequence, the different myosin head conformations illustrated in Figure 18.22 are the likely changes that would occur during a microcontraction cycle.
To help you follow the sequence find and follow the small dot on a single monomer in the actin filament. Here are the steps:
a) Calcium is required for contraction; in the presence of \(\rm Ca^{++}\) ions, myosin-binding sites on actin are open. (\(\rm Ca^{++}\)-regulation of muscle contraction is discussed in detail shortly.)
b) Myosin heads with attached ADP and Pi bind to open sites on actin filaments.
c) The result of actin-myosin binding is an allosteric change in the myosin head, which bends a hinge region to pull the attached microfilament. (Note the dot—it has moved to the left!) This micro-sliding of actin along myosin is the power stroke. The myosin head remains bound to an actin monomer in the F-actin.
d) ATP displaces ADP and Pi on myosin heads in this bent conformation. The resulting allosteric change in the head breaks the crossbridge between it and the actin.
e) Once dissociated from actin, myosin heads catalyze ATP hydrolysis, resulting in yet another conformational change. The head, still bound to ADP and Pi, has bent at its hinge, taking on a high-energy conformation that stores the energy of ATP hydrolysis.
Microcontraction cycles of actin sliding along myosin continue if ATP and \(\rm Ca^{++}\) are available. During repetitive microcontraction cycles, myosin heads on the thick filaments pull actin filaments attached to Z-lines, as stored free energy is released during power strokes, bringing the Z-lines closer together. The result is the shortening of the sarcomere, the muscle cells, and ultimately of the entire muscle. When the muscle no longer needs to contract, the \(\rm Ca^{++}\) required for contraction is withdrawn; microcontraction cycles cease; the myosin heads remain in the high-energy conformation of step e, and the muscle can relax (stretch). Neural stimulation can cause another release of \(\rm Ca^{++}\) that will again signal contraction.
The microcontraction cycle also stops when ATP is gone, the permanent state of affairs brought about by rigor mortis after death! At this time, myosin heads remain attached to the actin filaments in the state of muscle contraction that existed at the time of death. This is rigor at the molecular level (shown in the illustration above). At the level of whole muscle, rigor mortis results in the inability to stretch or otherwise move body parts when ATP has once-andfor-all departed. You will have encountered this phenomenon if you watch any police or detective story that includes a coroner!