Cytoskeltal Motors

Network of long protein strands located in the cytosol not surrounded by membranes

Consist of microtubules and microfilaments

Microfilaments protein threads of actincell movement and muscle contraction

Microtubules : help in movement of organelle around made up of tubulin

longest strands of cytoskeletonmake up spindle fibers (role in mitosis and meiosis)

 

Cytoskeletal motors

Motor  proteins  utilizing  the cytoskeleton for movement  fall  into  two  categories  based  on their substrates: •Actin motors such  as  myosin  move long microfilaments through  interaction with actin.•Microtubule motors  such  as  dynein  and kinesin  move  along microtubules  through interaction with tubulin.

Cytoskeletal motors

– Myosin is responsible for muscle contraction

– Kinesin moves cargo inside cells away from the nucleus along microtubules track.

– Dynein transports cargo along microtubules towards the cell nucleus.

MYOSIN MOTORS

Structure of a Muscle Cell

• Vertebrate muscle that is under voluntary control has  a  banded  (striated)  appearance  when examined under a microscope.

• It  consists  of  multinucleated  cells  that  are bounded by plasma membrane.

• A  muscle  cell  contains  many  parallel  myofibrils, each about 1 mm in diameter.

• The functional unit, called a sarcomere, typically repeats every 2.3 mm (23,000 Å) along the fibril axis in relaxed muscle

Structure of Muscle Cell

Structure of a Muscle Cell

Skeletal muscle myofibril showing asingle sarcomere

• A dark A band and a light I band alternate regularly. The central region of the A band, termed the H zone, is less dense that the rest of the band. The I band  is bisected by a very dense, narrow Z line.

Sarcomere

• A  sarcomere  of  a  myofibril  consists  of  two kinds of interacting protein filaments. 

• The  thick filaments have diameters of about 15 nm (150 Å) and consist primarily of myosin.

• The  thin filaments have diameters of approximately 9 nm (90 Å) and consist of actin as well as  tropomyosin and the troponin complex.

Skeletal muscle myofibril showing asingle sarcomere

Sliding-Filament Model

• Muscle  contraction  is  achieved  through  the sliding  of  the  thin  filaments  along  the  length of the thick filaments, driven by the hydrolysis of ATP . 

Sliding-Filament Model

• Tropomyosin and the  troponin complex regulate this sliding in response to nerve impulses. 

• Under resting conditions, tropomyosin blocks the intimate interaction between mysosin and actin.

• A nerve  impulse  leads  to  an  increase  in  calcium ion concentration within the muscle cell. 

• A component of the troponin complex senses the increase in calcium and, in response, relieves the inhibition  of  myosin  -  actin  interactions  by tropomyosin.

Thick Filament: Myosin head domains at each end and a relatively narrow central region

Interaction of thick and thin filaments in skeletal-muscle contraction

Actin Is a Polar, Dynamic Polymer

• Actin  monomers  (often called  G-actin for globular) come together to form actin filaments (F-actin filament).

• The  structure  is  polar,  with discernibly  different  ends. One end is called the barbed (plus)  end,  and  the  other  is called  the  pointed  (minus) end.

Myosin Power Stroke

• Individual  myosin  heads  bind  the  actin  filament and undergo a conformational change (the power stroke) that pulls the actin filament. 

• After a period of time,  the myosin head releases the actin, which then snaps back into place.

• The complete cycle of ATP-binding, hydrolysis, and phosphate release is called the "power stroke" cycle

• All myosins are composed of a globular catalytic head domain, a converter and a lever arm.

• Conformational changes in the catalytic head are amplified  by  the  lever  arm  during  the  ATPase cycle through an ~ 70° rotation of the lever arm.

The 'powerstroke' cycle of (+)-end-directed myosins. (Myosin II, Myosin V motor)

Myosin motors are plus end motors

Step 1: At the end of the previous round of movement and the start of the next cycle, the myosin head lacks a bound ATP and it is attached to the actin filament in  a  very  short-lived  conformation  known  as  the  'rigor  conformation'.

Step 2: ATP-binding to the myosin head domain  induces a small conformational shift  in  the  actin-binding  site  that  reduces  its  affinity  for  actin  and  causes  the myosin  head  to  release  the  actin  filament.  

Step 3: ATP-binding also causes a large conformational shift in the 'lever arm' of myosin  that  'cocks'  the  head  into  a  position  further  along  the  filament.  ATP  is then hydrolysed, but the inorganic phosphate and ADP remain bound to myosin.

Step 4: The myosin head makes weak contact with the actin filament and a slight conformational change occurs on myosin that promotes the release of inorganic phosphate.

Step 5: The  release  of  inorganic  phosphate  reinforces  the  binding  interaction between myosin and actin and subsequently triggers the 'power stroke'. 

Step 6: As myosin regains its original conformation, the ADP is released, but the 

myosin head remains tightly bound to the filament at a new position from where it started, thereby bringing the cycle back to the beginning.

           The complete cycle of ATP-binding, hydrolysis, and phosphate release is called

the "power stroke" cycle

Refer to following link for animation:

http://highered.mcgraw-hill.com/sites/0072495855/student_view0/

chapter10/animation__breakdown_of_atp_and

_cross-bridge_movement_during_muscle_c

ontraction.html