Skeletal Muscle Structure

Skeletal Muscle

40% of body weight, composed of multinucleated myofibers (single muscle cell)

surrounded by membrane structures: SR (form of ER, sequesters calcium) and transverse tubules

striated

Z-lines (Zwischen) – determines boundary of sarcomere
A-bands (anisotrophic) – dark, contain myosin
I-bands (isotrophic) – light, contain no myosin (only actin)

two types of fibers: hexagonal arrangement of thin (actin, tropomyosin, troponin) around thick (myosin)

Myosin

mechanoenzyme (converts ATP to movement)

like dynein (flagella/cilia, mitotic chromosomal separation) and kinesin (nerve axonal transport, mitosis)

dynein to nucleus (-), kinesin to membrane (+)
these both move on microtubules, whereas myosin contacts microfilaments (actin)

complex family of cell-type specific myosin isoforms divided into two broad categories

(1) conventional (type II) – all muscle types, heads in all directions, enabling crossbridges

also includes nonmuscle conventional myosin (furrow separating daughter cells)

(2) non-conventional (I, III, V, etc.) – neuron (vesicle support) and intestinal epith.(structure of microvilla)

can be isolated from muscle cell by high salt (0.6M KCl)

long rodlike tail (enables assembly) and globular head ("S1" – involved in generation of contraction)

monomer of six subunits (two 200 kD heavy chains, two 16 kD and two 20 kD light chains)

N-terminal region of heavy chains forms head, C-terminal region makes alpha-helical coiled-coil tail
light chains associate with head
these can be separated by proteases

Other Proteins in Myofibril

actin – highly conserved (95% mammal-ameba), G and F forms (use ATP to polymerize into two start helix)

has polarity and interacts with myosin head in specific direction

tropomyosin and troponin – bind to actin to form filaments (regulate contraction via calcium)

tropomyosin – elongated alpha helix coiled coil (like myosin tail) that binds actin filaments along grooves
troponin – three subunits (Tn-I, Tn-C, Tn-T) attach to thin filament with periodic spacing
one tropomyosin, Tn-I, Tn-C, and Tn-T per seven actin

alpha-actinin – anchors actin filaments to Z-disk

desmin and vimentin (perpendicular) – intermediate filaments; connect between Z-disk of adjacent myofibers

titin (2000-3500 kD) and nebulin (650-850kD) (parallel) – extend along sarcomere for strength (titin also in cardiac)

titin contains hundreds of 100-residue repeats (type III-fibronectin-like and C2-immunoglobulin-like)
nebulin – determines thin filament length (molecular ruler); prevents overstretching

thick filament associated proteins

C-protein (in A-band – 43nm stripes) repeats like titin (fast, slow, and cardiac isoforms)

M-prot (myomesin) – in M band of skeletal and cardiac myofibrils

tropomodulin – terminus of each thin filament (bind tropomyosin—may stabilize end of thin filament)

dystrophin – rodlike structural protein with globular domains at each end—may anchor myofibrils

Duchenne's Muscular Dystrophy (DMD, incidence 1/3500) from defect in dystrophin
Becker's Muscular Dystrophy – less severe form from defects in associated glycoproteins

creatine kinase – replenish ATP supplies during contraction (associated with M-line of thick filament)

skeletal and cardiac isoforms different (measure in bloodstream to determine heart (MI) or muscle (MD))

Process of Contraction

actin/myosin form stable crosslinkages (rigor complex) – broken by addition of ATP and Mg⁺⁺

myosin has actin-activated ATPase (increases ATP hydrolysis 300X)

four steps: attach (actin to myosin), release (ATP bind myosin), myosin cock (ATP hydrolysis), power stroke (myosin binds actin elsewhere, P_i then ADP released)