Contractile Proteins Flashcards
The Cytoskeleton
Define the stability, structure, shape, and is very dynamic
Structural, spatial and mechanical functions of cells depend on the cytoskeleton, a remarkable system of filaments scaffolding the cell
Actin
major compotent of the cytoskeleton
each subunit is called a G actin (globular)
has a tightly associated ATP or ADP
they polymerize head to tail to form a right handed helix called a filamentous actin (microfilaments) or F actin
filaments are polar with a slower growing minus end and a faster growing plus end
important in establishing myosin movement relative to actin
Assembly of actin polymers
small oligomers are unstable until they form an initial aggregate (3 monomers)
3 phases: nucleation, elongation, steady state
Process of assembly and dissasembly
actin has a bound ATP and it is hydrolyzed to ADP and Pi following assembly
ATP not necessary but ATP makes the process much faster
can also depolymerize as needed
an equillibrium exists between actin monomers and filaments and is dependant on the concentration of free monomers
Critical concentration
rate of actins polymerization into filaments is equal to the rate of dissociation
this is considered equilibrium
equation of polymerization of Actin monomers
k off = C x k on
C=the concentration of free monomers
k on is dependant of the concentration and that is the rate of association
k off is independant of the C and is the rate of dissociation
what makes up the 3 D structure of Actin filaments
THe actin filaments are organized into higher order structures that are regulated by actin binding proteins
Where are actin filaments particulary abundant
beneath the plasma membrane
where they provide mechanical support, detemine the cell shape, and allow movement of the cell surface allowing for cells to migrate and engulf particles and divide
What are three cross linking proteins of actin filaments
alpha-actin
filamin
spectrin
Actin bundles
cross link into closely packed parallel arrays
polarity of actin filaments
consist of Parallel bundles
and contractile bundles
Parallel bundle
closely spaced actin filaments in parallel
fimbrin monomer binds to actin filaments
has 2 actin binding domains
holds two parrallel filaments close together
increases the cell surface area allowing for additional receptors and channels which facillitated signaling transport and uptake of nutrients
supports projections of plasma membranes like microvilli
Contractile bundles
loosely bundled actin filaments
alpa-actin
this is a bigger protein so it allows for the filaments to be seperated by a greater distance
allows motor protein to interact during contraction
contractile ring used in mitosis
filamin
binds actin as a dimer and helps create a 3D meshwork
present in cells that need to withstand forces
filopodia
thin projections of the plasma membrane supported by actin bundles
Lamellipodia
broad sheet like extensions at the leading edge of cell, containing a network of actin filaments
Pseudopodia
based on actin filaments cross linked into a 3-D network, responsible for phagocytosis
Erythrocytes
have a strong cytoskeleton consisting of spectrin, ankrynin, and protein 4.1
important for the three dimensional shape of the erythrocyte
Hereditary Spherocytosis
mutation in the erythrocyte cotrical cytoskeleton proteins: Spectrin, ankyrin, Protein 4.1
impaired deformabillity
makes the RBCs spherical leading to membrane breakdown and Damge to RBCs
not bi-concave
anemia, jaundice, splenomegaly
Myosin
Motor protein
move along actin filaments via ATP hydrolysis
Skeletal Muscle Myosin II
three major parts of Myosin
Head: contains the actin binding and ATP binding sites, also has ATPase activity
Neck: Flexible region
binds myosin light chain peptides
Tail: intertwine to bring myosin head regions in close proximity
bind membrane/organelles
Myosin I
has only one head
one heavy chain
one light chain
function is for membrane association, and endocytosis
Myosin II
2 heavy chain
2 light chain
used for contraction (muscle)
Myosin 5
used for organelle transport
2 heavy chain
6 light chain
at the tail has a receptor that binds to a signal on a organelle
Process of movement of the myosin along F actin
1) Binds ATP and the head dissociates from actin
2) hydrolysis of ATP to ADP and Pi and the myosin cocks its head
3) Myosin binds the actin filament
4) release of the Pi causes a straightening of the bound myosin causing the power stroke moving the myosin
5) ADP released and the whole process restarts
WHat is the velocity of the powerstroke based on
velocity of the movement is proportional to the length of the neck
longer neck the faster the movement
THick filaments composed of:
6 myosin polypeptide chains
THin filament composed of
actin, tropomyosin, and troponin
important proteins in sarcomere
CapZ- binds the actin on the plus end
Tropomodulin- bind to the minus end of the actin
Nebulin- caps the minus end to prevent disassembly
Titin- gives more contractillity
Contraction of smooth muscle
similar to skeletal but the smooth doesnt have tropomyosin but has calmodulin
calcium binds calmodulin which causes a conformational change which will bind to myosin light chain and then will phosphorylate to the active myosin light chain and that will cause the power stroke
dephospho form does not
Non muscle cell contraction
much less stable or organized
cytokinesis
bundles of F actin and myosin form contractile ring
alpha actinin
myosin moving along causes the pinching
Dystrophin
links the cytoskeleton of muscle fibers to the surrounding connective tissue and the extracellular matrix
this interaction acts as a shock absorber
stabilizes the sarcolemma
connects the PM to the actin filaments
Duchene Muscular Dystrophy
X linked recessive disorder
abnormal dystrophin
progressive muscle wasting
wheelchairs by age 12 and die of respiratiry failure by age 22
Milder form with later onset Becker muscular dystrophy
how is dystrophin disrupted
DMD are out of frame mutations- little to no expression of dystrophin
BMD: in frame mutation- smaller protein with partial function
large internal deletions and lead to muscle degeneration
gene therapy
dystrophin replacement
