Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

MYOSIN AND ACTIN
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muscle: its myosin II hydrolyzes ATP about 10 times more slowly than skeletal
muscle myosin, producing a slow cycle of myosin conformational changes that
results in slow contraction.
Heart Muscle Is a Precisely Engineered Machine
The heart is the most heavily worked muscle in the body, contracting about 3 billion
(3 × 10 9 ) times during the course of a human lifetime (Movie 16.6). Heart cells
express several specific isoforms of cardiac muscle myosin and cardiac muscle
actin. Even subtle changes in these cardiac-specific contractile proteins—changes
that would not cause any noticeable consequences in other tissues—can cause
serious heart disease (Figure 16–38).
The normal cardiac contractile apparatus is such a highly tuned machine
that a tiny abnormality anywhere in the works can be enough to gradually wear
it down over years of repetitive motion. Familial hypertrophic cardiomyopathy is
a common cause of sudden death in young athletes. It is a genetically dominant
inherited condition that affects about two out of every thousand people, and it is
associated with heart enlargement, abnormally small coronary vessels, and disturbances
in heart rhythm (cardiac arrhythmias). The cause of this condition is
either any one of over 40 subtle point mutations in the genes encoding cardiac β
myosin heavy chain (almost all causing changes in or near the motor domain) or
one of about a dozen mutations in other genes encoding contractile proteins—
including myosin light chains, cardiac troponin, and tropomyosin. Minor missense
mutations in the cardiac actin gene cause another type of heart condition,
called dilated cardiomyopathy, which can also result in early heart failure.
Figure 16–38 Effect on the heart of a
subtle mutation in cardiac myosin. Left,
normal heart from a 6-day-old mouse
pup. Right, heart from a pup with a point
mutation in both copies of its cardiac
myosin gene, changing Arg403 to Gln.
The arrows indicate the atria. In the heart
from the pup with the cardiac myosin
mutation, both atria are greatly enlarged
(hypertrophic), and the mice die within a
few weeks MBoC6 of birth. m16.79/16.38
(From D. Fatkin et al.,
J. Clin. Invest. 103:147–153, 1999. With
permission from The American Society for
Clinical Investigation.)
Actin and Myosin Perform a Variety of Functions in Non-Muscle
Cells
Most non-muscle cells contain small amounts of contractile actin–myosin II bundles
that form transiently under specific conditions and are much less well organized
than muscle fibers. Non-muscle contractile bundles are regulated by myosin
phosphorylation rather than the troponin mechanism (Figure 16–39). These
contractile bundles function to provide mechanical support to cells, for example,
by assembling into cortical stress fibers that connect the cell to the extracellular
myosin light chains
actin-binding site
ATP ADP P P
PHOSPHORYLATION
BY MLCK
SPONTANEOUS
SELF-ASSEMBLY
bipolar filament
of 15–20 molecules
myosin tail released
INACTIVE STATE:
(light chains not phosphorylated)
ACTIVE STATE:
(light chains phosphorylated)
(B)
1 µm
(A)
Figure 16–39 Light-chain phosphorylation and the regulation of the assembly of myosin II into thick filaments. (A) The controlled
phosphorylation by the enzyme myosin light-chain kinase (MLCK) of one of the two light chains (the so-called regulatory light chain, shown in light
blue) on non-muscle myosin II in a test tube has at least two effects: it causes a change in the conformation of the myosin head, exposing its actinbinding
site, and it releases the myosin tail from a “sticky patch” on the myosin head, thereby allowing the myosin molecules to assemble into short,
bipolar, thick filaments. Smooth muscle is regulated by the same mechanism (see Figure 16–37). (B) Electron micrograph of negatively stained short
filaments of myosin II that have been induced to assemble in a test tube by phosphorylation of their light chains. These myosin II filaments are much
smaller than those found in skeletal muscle cells (see Figure 16–27). (B, courtesy of John Kendrick-Jones.)
MBoC6 m16.72/16.39