Topic 30: Myosin & Actin

Myosin II

• is a prototypical actin-based motor protein

• a myosin II complex has 2 heavy chains

Myosin II: terminal head domains are what?

• the motor domains

Myosin II: light chains are what?

• regulatory subunits

What do the C-terminal helices in Myosin II form?

• coiled-coil mediating self-assembly

Muscle myosin II self-assembles into what?

• large “thick filmanets”

what are bipolar filaments made up of?

• made up of many dimers oriented in opposite directions on either side of the bare zone

What is the bare zone?

• portion in the middle of the filament with no myosin heads

Is myosin II a (+) or (-) end-directed actin motor protein?

• plus end-directed

Which way do the myosin motor domains (heads) move/pull?

• pull the (+) end of the actin filament towards themselves, sliding the actin

• move/walk towards the (+) end

which end does the Myosin II walk?

• walks towards the (+) end of actin filaments taking steps of defined size

If the myosin II is anchored, which way does it slide the actin filament?

• slides the actin filament, pulling the plus end towards itself

Sarcomere

• repeating cytoskeletal structure in myofibrils

• ordered arrays of myosin thick filaments and actin thin filaments

Where do myosin thick filaments slide the actin thin filaments?

• towards the center

CapZ

• caps the plus end of the actin filament

tropomodulin

• caps the minus end of the actin filament

Nebulin & titan

• function as molecular rulers

• titan also functions as molecular spring

T tubules

• propagate an electrical contraction signal into the interior of the muscle cell

• its an invagination of plasma membrane; lumen (interior) of tubule is extracellular space

• T-tubule and SR are very closely juxtaposed

what does the electrical depolarization of T-tubule membrane trigger?

• triggers massive Ca2+ release

Pathways of electrical depolarization

lumen of T-tubule —> voltage-gated Ca2+ channel —> Ca2+ release channel —> huge Ca2+ release from sarcoplasmic reticulum

what happens when calcium binds to the troponin complex?

• its shifts the location of tropomyosin exposing myosin binding sites

tropomyosin

• binds all along the actin filaments, blocking access to myosin binding site when Ca2+ is low

Ca2+ binds to troponin C, a calmodulin-like subunit, triggering what?

• a conformational shift

What does calmodulin transduce?

• transduces GPCR signaling into smooth muscle contraction via myosin light chain kinase

what does myosin light chain phosphorylation activate?

• myosin II

The activity of on-muscle myosin II is also regulated by what?

• myosin light chain kinase

What activates Myosin light chain kinase (MLCK)?

• activated by several different pathways often involving Rho GTPase

Myosin V

• well adapted to carry cargo along actin filaments

  • has a long lever arm = long steps

  • each motor domain stays bound to actin filament for linger than myosin II (many steps before “falling off”)