Sarcomere Structure Flashcards
What is the structure of striated muscle?
• Whole muscle is made up of bundles of fascicles
• Each fascicle is made up of a series of fibres
• Each fibre made up of elements called
myofibrils
• Each myofibril made up of repeating units (sarcomeres) consisting of interdigitating filaments (myofilaments)
Discuss muscle development
- Myosatellite cells (mesenchymal cells) in each myotome give rise to myoblasts (mononuclear skeletal muscle precursors) , which mature into myocytes (multinucleated cells)
- Myotubes synthesise contractile proteins to form myofilaments
- Myostatin inhibits this process of differentiation
Discuss the structure of sarcomere
- Sarcomeres are highly organised within skeletal & cardiac muscle and give a striped appearance – striated muscle
- A sarcomere is the portion of a myofibril that lies between two successive Z disks
- Contractile proteins
What contractile proteins are present in sarcomeres?
• Thin filaments (actin protein - 5-8nm dia; 1
μm length)
• Thick filaments (myosin protein - 10nm dia, 1.6 μm length)
• I band (isotropic) represents actin filaments
• A band (anisotropic) represents myosin filaments
What are the structural proteins of sarcomere?
- α-actinin
- Titin
- Nebulin
- Dystrophin
What role does α-actinin play in sarcomere?
– Part of spectrin family of actin-binding proteins
– Binds end of thin filaments to Z discs
What role does titin play in sarcomere?
– largest known protein (approx. 25,000 aa)
– Binds end of thick filaments (M line) to Z discs
– different titin isoforms
- leads to different elasticity of different muscle types
What role does nebulin play in sarcomere?
– actin-binding protein which is localized to the I-
band
– large protein (600-900 kDa) and binds as many as 200 actin monomers
– thin filament “ruler” and regulates thin filament length during sarcomere assembly
What role does dystrophin play in sarcomere?
– Large protein associated with Z disks
– Helps align Z disks with disks in adjacent myofibrils
What is present in the I band of a sarcomere?
thin filaments only
What is present in the H zone of a sarcomere?
thick filaments only
What is present in the M line of a sarcomere?
thick filaments linked with accessory proteins
What is present in the outer edge of the A band of a sarcomere?
thick and thin filaments overlap
What are thin filaments in sarcomere made of?
• Thin filaments consist of 3 proteins
– Actin
– Tropomyosin
– Troponin
What is the structure of thin filaments in sarcomere?
- Backbone is double-stranded α-helical polymer of actin molecules (F-actin)
- Tropomyosin molecules consist of 2 identical α-helices, coil around groove formed by actin
What is tropomyosin?
– Regulatory protein
– Overlaps binding sites on actin for myosin and inhibits interaction when in the relaxed state
What is troponin?
a heterotrimer
– Troponin T (binds to tropomyosin)
– Troponin I (binds to actin and inhibits contraction
– Troponin C (binds Ca2+)
– Ca2+ binding to troponin regulates skeletal muscle contraction because it moves the tropomyosin away and allows myosin to interact with the actin
What does Ca2+ binding to troponin do?
regulates skeletal muscle contraction because it moves the tropomyosin away and allows myosin to interact with the actin
What are thick filaments in sarcomere?
• Thick filaments are bipolar assemblies of multiple myosin-II molecules
What is myosin-II made of?
• Each myosin-II molecule consists of
– 2 intertwined heavy chains
– 2 regulatory light chains (MLC-2) (regulates ATPase activity of myosin)
– 2 essential light chains (MLC-1) (stabilizes myosin head)
– Structural related to calmodulin siperfamily
How does Ca2+ modulate contraction?
through regulatory proteins rather than direct interaction with contractile proteins
What occurs to regulatory proteins in cross bridge cycling without Ca2+?
regulatory proteins act to inhibit actin-myosin interactions
What role does troponin C play in the initiation of cross bridge cycling?
• Troponin C is key Ca2+ sensitive regulator
– 2 high affinity binding sites (help in binding troponin C to thin filament)
– 2 low affinity binding sites (binding of Ca2+ to these sites brings about conformational change in troponin complex)
Describe the initiation of cross bridge cycling
- When [Ca2+]i rises and Ca2+ binds to TnC a conformational change of proteins occurs
- Troponin I moves away from actin filament
- Troponin T pushes tropomyosin away from actin binding site
- As long as Ca2+ is present, multiple cross-bridges cycles can occur and muscle shortens
- When [Ca2+]i falls, Ca2+ dissociates from TnC leading to a reversal of the conformational change
