Abstract
Author SummaryThe contraction and relaxation cycles of active muscles generate substantial mechanical forces, both axially and radially, that place extraordinary stress on the molecular structures within the muscle fibers. These forces are sensed and buffered by unusually long and elastic filament proteins with highly repetitive domain structures. Myomesin is one such repetitive filament protein that is thought to form bridges between the main contractile filaments of the muscle, providing the muscle structure with resistance in the radial dimension. To investigate how the repetitive structure of myomesin contributes to muscle elasticity, we determined the overall architecture of its complete repetitive domain array using a combination of four complementary structural biology methods. Our study reveals a long, dimeric tail-to-tail filament structure folded into an irregular superhelical coil arrangement of almost identical domain modules separated by short linkers. When we applied tension to these myomesin filaments, we found they could stretch to about 2.5 times their original length by unfolding these linkers, and then return to their original state when the tension was removed. Our findings explain how myomesin might adapt its overall length in response to the changing dimensions of the contracting and relaxing muscle, so acting as a highly elastic ribbon that maintains the overall structural organization of the muscle fibers. More generally, these findings demonstrate how repetitive domain modules, such as those in myomesin, can provide elasticity to highly organized biological structures.
Highlights
Striated myofibrils are found in skeletal and cardiac muscle cells and represent a highly organized cellular system for studying how active force can be generated while the overall structural organization of the underlying sarcomeric units is maintained
To investigate how the repetitive structure of myomesin contributes to muscle elasticity, we determined the overall architecture of its complete repetitive domain array using a combination of four complementary structural biology methods
Our study reveals a long, dimeric tail-to-tail filament structure folded into an irregular superhelical coil arrangement of almost identical domain modules separated by short linkers
Summary
Striated myofibrils are found in skeletal and cardiac muscle cells and represent a highly organized cellular system for studying how active force can be generated while the overall structural organization of the underlying sarcomeric units is maintained. The principal protein components of myofibrils are large longitudinal filaments that include actin (thin filament), myosin (thick filament), titin, and nebulin [1] These filaments form a well-established striated pattern of distinct zones, with the M-band at the center [2]. On activation, both substantial axial and radial forces are generated within the overall sarcomere structure [3]. Elastic Mband motions are thought to correlate with heart beat rate [5], rendering investigations of the underlying molecular parameters highly relevant to heart and skeletal muscle research
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have