32: Contractile Proteins Flashcards
Dystrophin function
Links muscle fiber cytoskeleton + ECM/basal lamina; acts as a shock absorber for contraction, stabilizes sarcolemma
Dystrophin structure
Super big; 427 kDa (largest human gene, 79 Exons), has numerous redundant coils
What are 2/3rds of all dystrophin mutations
Large internal deletions
Out of frame vs in-frame dystrophin mutation
Out of frame -> frameshift -> DMD
In frame -> BMD
Genetics of DMD
X-linked recessive, affecting 1 in 3,500 boys
A few treatment options for DMD
Gene therapy, dystrophin replacement, drugs to prevent exon skipping
G actin structure
375AA polypeptide divided into two lobes, with an ADP or ATP bound to the bottom of the cleft, connecting the lobes
F actin
Tight right-handed helix formed by two strands of G actin polymerizing
Why is polarity of actin important?
For determining which way myosin moves along it
Three steps of actin filament assembly
- Nucleation
- Elongation phase
- Steady state
Nucleation of actin
3 G-actin monomers aggregate into an oligomer
ATP hydrolysis in actin formation
ATP is bound to monomers -> hydrolyzed to ADP + Pi following filament assembly
Where are actin filaments particularly abundant in the cell?
Beneath plasma membrane
A requirement for actin binding proteins
Must have at least two actin-binding domains (ABDs)
Actin bundles vs actin networks
Actin bundles: cross-linked into parallel arrays (filament polarity aligned)
Actin networks: loosely cross-linked into orthogonal arrays (polarity doesn’t align)
Two types of actin bundles and the protein that holds them together
- Parallel bundles: fimbrin
2. Contractile bundles: a-actinin
Parallel vs contractile bundles of actin: packing
Parallel bundles: tight packing -> prevents myosin II from entering
Contractile bundles: loose packing, allowing myosin II to enter for contraction
Parallel bundle function
Supports projections of plasma membrane, increases cell surface, structural stability, allows for additional receptors to be placed on plasma membrane