Schematic representation of the sarcomere. The z line is depicted in black, myosin in green/grey, actin in red and tropomyosin in blue. MPI of Molecular Plant Physiology
contraction and many other movement processes are controlled by the
interplay between myosin and actin filaments. Two further proteins,
tropomyosin and troponin, regulate how myosin binds to actin. While
theoretical models have in fact described exactly how these muscle
proteins interact, this interaction has never previously been observed
in detail. Stefan Raunser and Elmar Behrmann from the Max Planck
Institute of Molecular Physiology in Dortmund have now managed to image
the actin-myosin-tropomyosin complex with an unprecedented accuracy of
0.8 nm, which amounts to a resolution of less than one-millionth of a
millimeter. This has, for the first time, made it possible to correctly
identify the location of proteins within the complex and to analyse the
processes involved in muscle contraction. These findings could help
determine the impact of genetically determined modifications to the
actin-myosin-tropomyosin complex in certain types of hereditary heart
basic functional unit of a muscle, known as the sarcomere, consists of
actin, myosin and tropomyosin proteins. If a muscle is to be able to
contract, the myosin must slide along filamentous actin molecules.
Working together with troponin, tropomyosin regulates muscle contraction
by controlling when myosin binds to actin. In the resting state,
tropomyosin and troponin block the binding site for myosin on the actin
filament. At this point, the myosin head is at a 90-degree position.
Only after an influx of calcium, which docks onto the regulating
proteins, is the binding site on the actin filament exposed. The myosin
head docks onto this site, changes its conformation and bends in an
articulated manner, thereby pulling the actin along with it. As the
filaments slide over one another, the sarcomere shortens and the muscle
from the Max Planck Institute of Molecular Physiology in collaboration
with scientists from Hannover Medical School, Ruhr-Universität Bochum
and the University of Texas in Houston, have now, for the first time,
been able to reveal the details of the interaction on which this model
is based. Thanks to improved electron microscopy techniques, Stefan
Raunser and his colleagues have also, for the first time, gained an
accurate insight into the structural elements of muscle.
is an important step in understanding the interplay between the
individual proteins within the functional structures of muscle,” says
scientists were able, for example, to identify the exact location of
tropomyosin on the actin filament in the myosin-bound state and, with
their detailed imaging of the complex’s structure, showed that actin
actually brings about conformational changes in myosin. Comparisons with
myosin structures in other states have allowed the researchers to
describe the interplay of myosin and actin during muscle contraction.
have, so to speak, drawn a map for biochemists. Our findings will make
it easier for them to understand the processes and sequences of events
taking place in muscles,” explains Raunser.
findings are also highly relevant from a medical standpoint. The human
heart is the body’s most important muscle and, if it is working at less
than its best, the outcome can be fatal. Malfunctions within the heart
are often associated with point mutations. The micrographs taken by the
Max Planck researchers have now made it possible to identify the exact
location of these mutations for the first time.
“Finding the exact location of the mutations is fundamental to developing treatments for such heart diseases,” says Raunser.