Contractile Proteins and Muscle Diseases Flashcards
Describe the electron micrograph of a single myosin molecule
Two-headed structure with a long, thin tail
What are the thick and thin filaments associated with the contractile apparatus in skeletal muscle?
Thin filaments = actin
Thick filaments = myosin
Actin are anchored by Z-discs; 6 thin filaments surround each end of 1 thin filament
Describe the bipolar assembly of myosin
Bipolar assembly refers to self-assembly at the tails.
Myosin filaments arranged with tails facing each other (middle = bare zone), tails are coiled coil of 2 alpha helices, light chains and N terminus located near heads at hinge region
_______ makes up 35% of total protein in muscle cells
Myosin
Myosin is made up of ____ polypeptide chains:
_____ heavy chains + ______ light chains
It has a _______ rod domain and _____ globular heads
6
2; 4
Helical; 2
Which region of myosin hydrolyzes ATP
Head region
The myosin heads are at _____ degrees rotational symmetry and the surrounding thin filaments are at _____ degrees rotational symmetry
30; 60
Treatment of muscle myosin with proteases like _______ or ________ creates stable fragments
Papain; trypsin
[papain cleaves at hinge region, trypsin further down the tail]
The myosin tails are arranged in a coiled-coil formation, and with every turn you have _________ residues interacting
Hydrophobic
The structure of the S1 fragment (head and neck region) of myosin exhibits a _______ ______ domain
P-loop ATPase
The structure of the S1 fragment (head and neck region) of myosin exhibits a P-loop ATPase domain. The P-loop serves as the ______ binding site, while the _______ binding site is closer to the head
Nucleotide; actin
The structure of the S1 fragment (head and neck region) of myosin exhibits a P-loop ATPase domain. What 2 types of light chains are associated with the neck region?
Essential light chain
Regulatory light chain
Part of the myosin molecule moves dramatically (essential light chain and regulatory light chain in neck region) in response to what?
What is the significance of this?
ATP binding, hydrolysis, and product release
This is what propels myosin along an actin filament!
What region of the sarcomere corresponds to actin filaments only?
I band
What region of the sarcomere contains both myosin and actin?
A band
What protein is responsible for anchoring actin filaments at the ends of each sarcomere?
Z-disc
What protein is responsible for anchoring myosin to portions of the z disc?
Titin
What protein links the bipolar assembly of myosin together?
Myomesin 1 (aka M protein)
Characterize the directionality of actin
Minus end = pointed end
Plus end = barbed end - this is what sticks to the z-disc
_______-actin assembles into _______-actin (or filamentous actin), which exists in a ______ ______ arrangement with 2 parallel strands that twist around each other.
G; F; double helical
Each G-actin monomer interacts with ____ neighbors. The growing and the final filament exhibits directionality (plus and minus end).
ATP binds ____ G-actin first. The mature filament contains _______ bound to the monomeric G-actin units
Four
Free; ADP
Which end of actin attaches to the z-disc?
Plus end (barbed end)
The size and position of the actin filament is controlled by several proteins.
_______ caps the minus end (not at Z-disc), preventing further polymerization
Tropomodulin
The size and position of the actin filament is controlled by several proteins.
_________ (or beta-actinin, a heterodimer), which associates with alpha-actinin, caps at the plus end
CapZ
The size and position of the actin filament is controlled by several proteins.
_______ (6,669 residues): “ruler” and template for actin polymerization
Nebulin
____________ binds tropomyosin; positions the complex on the filament
Troponin T
__________ binds actin; inhibits myosin binding
Troponin I
_________ binds Ca and relieves inhibition
Troponin C
What protein assists in formation of contractile bundle at Z disc - forming bridges between adjacent thin filaments?
Alpha-actinin
Indirect immunofluorescence micrographs of isolated sheets of skeletal muscle Z discs using antibodies to alpha-actinin show that it occurs at the _______ of the Z disc
_______ protein is distributed about the Z-disc periphery
Interior
Desmin
Dystrophin is a 2400 kb gene with 3685 amino acid residues and 79 exons. There are numerous isoforms. What accounts for C-termini vs. N-termini variability?
C-termini variability: Alternative exon splicing
N-termini variability: Alternative transcription initiation sites
Dystrophin is in the same protein family as what other 2 important proteins?
Alpha-actinin
Spectrin
Duchenne Muscular Dystrophy and Becker Muscular Dystrophy result from what genetic event?
Exon deletions (may also be exon duplications but that is less common)
What is the difference between DMD and BMD?
Duchenne muscular dystrophy - no detectable dystrophin
Becker muscular dystrophy - dystrophins of various sizes
What is the inheritance pattern for DMD?
X-linked recessive