Myosin-based Molecular Motors (L9) Flashcards
What are the 3 types of muscle?
Which one is the most primitive?
Which types are striated?
Cardiac, smooth (most primitive), and skeletal muscle.
Cardiac and skeletal muscle are striated.
What makes up a muscle cell?
Muscle cells consist of myofibrils which consists of linearly linked SARCOMERES which give muscle a striated appearance.
What are the majore proteins in a sarcomere and what is each protein for?
Myosin: Primary thick filament protein
Actin: Primary thin filament protein
Actinin: Anchors thin filaments to z disc
Titin: Connects z disc to thick filaments
Nebulin: Acts as molecular ruler to regulate length
Dystrophin: Anchors array of myofibrils to plasma membrane
Mneumonic: DAMN TA
What are the 6 polypeptides of striated muscle myosin (myosin II)?
2 heavy chains
2 essential light chains
2 regulatory light chains
What are the 3 main fragments of myosin yielded when treated w/ papain and trypsin?
What are their functions?
- 2 S1 sub fragments (N-terminal portion of heavy chain, 1 essential light chain, 1 regulatory light chain): it is the motor
- An S2 fragment
- A light meromysin fragment
Both 2&3 contain portions of the 2 heavy chains that form the coiled-coil tail of the intact myosin molecule.
What part of the S1 fragment is the binding site for the 2 light chains?
The P-loop NTPase domain: the alpha helix that extends from this domain is the binding site.
The essential and regulatory light chain are similar to what other protien?
How do they bind to the heavy chain?
Calmodulin protein.
All three homologous proteins binds the alpha helix of the P-loop NTPase domain of the heavy chain by wrapping around it.
What ions bind to the light chains?
What is true about the chains regarding function?
Ca2+ binds essential light chain
Mg2+ binds regulatory light chain
Calmodulin will bind calcium.
The primary function of the light chains are structural, not regulatory. Skeletal muscle light chains have lost most calcium binding properties.
Describe the process of the crossbridge cycle.
- Myosin in relaxed muscle is bound to ADP and Pi, and associates WEAKLY w/ actin
- Pi is released (regulated by Ca) and myosin binds to actin creating a “strong myosin crossbridge”
- ADP is releasted initiated the power stroke
- ATP binds to myosin and detaches it from actin
- ATP hydrolysis causes lever arm to lock in a relaxed position leaving ADP left with Pi on myosin.
What are the enzymes that performe these rxns?
1) ATP+Creatine ⇔ ADP+Phosphocreatine
2) ADP+ADP ⇔ AMP+ATP
1) Creatine Kinase
2) Adenylate Kinase
What are myosin I motors?
What is special abou their carboxyl terminal ends?
Myosin I ATPase activity is regulated by what?
They are single headed molecules lacking the coiled-coil carboxyl tail of muscle myosin. They attach to actin tracks (microfilaments) the same way Myosin II does to effectively drag the vesicles along the tracks.
The carboxyl terminal end is a lipid-binding domain that associates with vesicles.
ATPase Activity is regulated by Ser/Thr phosphorylation.
Regulation of smooth muscle contraction is ___ filament based.
Describe the regulation
Thick.
Calcium binds to calmodulin, which binds to myosin light kinase, which then hydrolyzes ATP and the Pi is transferred to myosin which can then perform the myosin crossbridge cycle.
Regulation of striated muscle contraction is ___filament based.
Describe this regulation.
Tropomysin blocks the myosin binding site on actin. Ca2+ will bind to Troponin which changes conformation, sliding tropomysin out of the way so myosin can access its binding site on actin.
Describe the structure of troponin.
Where will Calcium bind?
It is a trimer (TnC, TnT, TnI) with a calmodulin-like calcium-binding subunit.
Ca2+ ion will bind to TnC
What is considered low and high calcium concentrations?
Low: <10-7 M Ca2+ (Relaxed)
High: >10-6 M Ca2+ (Contracted)
