Dr. Seidler's Lectures on Contractile fibers Flashcards
Myosin is composed of
coiled coil of two alpha helices:
2 heavy chains and 4 light chains
N terminus, hinge region, and a minus end
bipolarity
N terminus/hinge region—-minus end
what pars of the myosin coiled coil’s associate?
the minus ends to form the bare zone
There are ____ heads, ____ chains, and one ____ domain in myosin
2 N terminus heads (globular)
2 heavy chains, 4 light chains
rod domain (helical)
Where does myosin self-assembly?
at the tails
Muscle tissue is “in register”: what does that mean?
the striations line up together to form larger striations
how many thin filaments surround a thick filament
6
what anchors the thin filament?
the Z disc, “anchored” to Z disc
There is a ____ degree of rotational symmetry of the thin filament around the thick filament
60 degrees
what gives the thick filaments the ability to stack AND move around?
the linker protein
myosin has _____ amino acids per turn
3.5
so there are 7 amino acids per 360 degrees?
7
What kind of amino acid would we expect to find in the interior of the myosin?
hydrophobic
rigor mortis
respiration doesnt occur, so oxidative phosphorylation isn’t occurring, so the thin filaments aren’t being dragged along by the head groups (the myosin needs the ATP): the myosin remains attached (does not dissociate)
what kind of disease leads to a point mutation in the code for myosin?
a dominant
how many possibe binding partners does an actin (thin) filament have?
4
Tropomodulin
caps the minus end of the thin filament (not the Z disc)
CapZ
b-actinin, a heterodimner which associates with a-actinin, caps at the plus end
Troponin complex
Troponin T, I, C
Troponin T
binds tropomyosin and positions the complex on the filament
Troponin I
binds actin, inhibits myosin binding
Troponin C
binds Ca, relieves inhibition
Tn-I
inhibitory troponin: has three isoforms found in tissues.
cTn-I is found in cardiac tissue and its serum levels rise after a myocardial infacrtion
cTn-I
the isoform of inhibitory troponin that appears in serum after an infarction
what method helps distinguish a myocardial infarction in the lab
an ELISA looking for cTn-I
TIC
three small troponin proteins that transduce the role of calcium in muscle contraction
what initiations contraction? ATP or Calcium?
Calcium
What troponin does calcium bind to?
troponin C
What actin monomer is in the assembled state?
G actin
What actin monomer is in the depolymerized state?
F actin
Pointed End
the end fixed to the Z disc
the barbed end
hanging in space
what are the proteins that make up the thin filaments?
actin, tropomysoin, regular intervals of the troponin complex
alpha-actinin =
make up proteins that arrange the actin monomers in the hexagonal arrangement
these are within the actin bundles of myofibrils
actins are held together at the Z discs by
alpha actinin
the myofibrils are held together by
desmin
Returning to the question of the myofibrils held in register, what does this?
the Z discs are all aligned two ways: a) the a-actinin anchors the actin at the designated point (the Z disc); these areas are then linked together by DESMIN
these then tether to costameres: these are tethering proteins to the sarcolemma
costamere protein
dystrophen, tethers the myofibrils to the sarcolemma
Titan
Sarcomere ruler
“molecular ruler”
BALANCES forces across the sarcomere. passive elasticity
muscle signaling
allows for elasticity without ripping
DHP channel
it’s responsive to the action potential, but it’s mechanically
DHP is voltage dependent that is mechanically gated: it opens (mechanically) the ryanodine receptor.
Hypocalcemic does what?
releases inhibition of the sodium channel and causes it to spontaneously fire
results in tetany
Myosin light chain kinases
smooth muscle lacks troponin complexes, so these proteins are activated by calmodulin (Ca activated): MLCK then phosphorylated myosin light chain, enabling a myosin crossbridge to bind to the actin filament and permit contraction
Calmodulin-MLCK
the main pathway for smooth muscle contraction
Duchenne muscular dystrophy
X linked, reessive disorder with an incidence of 1/3500 boys
progressive muscle wasting
result from mutations in dystrophen gene (costamere)
GSD V/McArdle disease
deficiency in muscle glycogen phosphorylase
autosomal recessive disease
deficiency in glycogen phosphorylase, rate limiting enzyme of glycogen degradation
cleaves glucose residues from glycogen for release as glucose-1 phosphate.
marked by myoglobin in the urine during intense exercise
individuals suffer immense fatigue because they can’t get glucose
GSD VI
mutations in chromosomes 14/11 cause mutations of phosphorylase = Hers Disease in the liver
GSD V versus GSD VI
GSD VI occurs in the liver.
GSD V is activated by AMP, Ca-Calmod, and G actin.
GSD VI is inactivated by glucose and no affected by AMP
both forms are activated by phosphorylation catalyzed by PhK
Duchene
no dystrophin
Beckers
truncated dystrophin
what does dystrophin do?
tether’s outer bundles of myofibrils to surface membrane
dystrophen is in the
carsomeres: helps withstand strenuous exercise
what happens if you didn’t have dystrophin?
your muscles would rip
What mediates the glycogen to glucose degradation in the liver?
glycogen phosphorylase
What mediates glucose-6-phosphate breakdown to pyruvate in the liver?
Glucose-6-Phosphatase
Glycogen Phosphorylase is activated by
AMP signaling
AMP binds to what site on Glycogen phosphorylase?
the “s” catalytic subunit (it’s the allosteric, not active site)
How is glycogen phosphorylase activated?
AMP bings to an allosteric site and a phosphorylase P’s a serine residue, increasing its activity
phosphorylase kinase
activated by calmodulin, it then activates glycogen phosphorylase
