Myosins

Overview of Microfilament-Based Transport

  • Actin microfilaments, like microtubules, function as intracellular “highways” for directed movement of materials.

  • Transport is not spontaneous; it requires specialized ATP-dependent motor proteins.

  • These motors convert the chemical energy of ATP hydrolysis into mechanical work, producing “power strokes” that propel cargo along actin filaments toward specific cellular destinations.

Myosin Motor Proteins: Family & Diversity

  • The primary actin-based motors are members of the myosin superfamily.

  • Current catalog: 2424 distinct myosin classes have been identified.

  • Each class is encoded by separate genes and tailored to unique cellular tasks (e.g., vesicle trafficking vs. muscle contraction).

  • Evolutionary note: sequence divergence is greatest in cargo-binding tail regions, allowing functional specialization while preserving a conserved actin-binding head.

Core Structural Features of Myosin

  • Head (Motor Domain)
    • Binds actin filaments.
    • Houses the ATPase catalytic site; ATP hydrolysis drives conformational changes that generate motion.

  • Neck / Lever Arm
    • Often stabilized by calmodulin or light chains.
    • Amplifies small movements in the head into larger steps along actin.

  • Tail (Cargo-Binding & Dimerization Domain)
    • Length and composition vary widely among myosin classes.
    • Determines:
    – Whether the molecule is a monomer or dimer.
    – What cellular cargo (membranes, vesicles, organelles, other proteins) it attaches to.

  • Visual cue from lecture: different myosins illustrated with dramatically different tail lengths—major structural hallmark that underlies functional diversity.

  • Informal aside from instructor: “look how cute they are” → emphasizes the recognizable lollipop-like shape.

Functional Roles of Myosin in the Cell

  • Muscle Contraction
    • Myosin-II thick filaments slide along actin thin filaments, shortening sarcomeres.
    • Classical cross-bridge cycle: Bind → Power-stroke → Release → Reset.

  • Cell Motility
    • Cytokinesis: myosin-II forms the contractile ring that pinches dividing cells.
    • Lamellipodia & filopodia: myosin-I contributes to membrane ruffling and forward protrusion.

  • Phagocytosis
    • Actin-myosin interactions generate forces that engulf pathogens/particles.

  • Vesicle & Organelle Transport
    • Myosin-V “walks” vesicles/organelles along actin cables toward the cell periphery.
    • Myosin-VI uniquely moves toward the minus end of actin, positioning endocytic vesicles near the cell center.

  • Tension Maintenance & Signal Transduction
    • Myosin-I links plasma membrane to cortical actin, regulating membrane tension and receptor organization.

Comparative Perspective: Myosin vs. Microtubule Motors

  • Energy Source: Both use ATP hydrolysis; mechanochemical cycle principles are conserved.

  • Track Polarity:
    • Actin filaments: plus (+) end at barbed edge, minus (−) end at pointed edge.
    • Microtubules: plus (+) end at periphery, minus (−) near centrosome.

  • Directional Bias:
    • Most myosins move toward the actin plus end; Myosin-VI is a notable minus-end exception.
    • Kinesins (microtubules) generally move plus-ward; dyneins move minus-ward.

  • Step Size:
    • Myosin-V: ≈ 36 nm36\,\text{nm} per step (matching actin pseudorepeat).
    • Kinesin-1: 8 nm8\,\text{nm} per step along microtubules.

  • Cargo Specificity mediated by divergent tail regions in both protein families.

Numerical & Statistical References

  • 2424 distinct myosin classes identified to date.

  • Step size example (Myosin-V): 36 nm36\,\text{nm}.

  • ATP hydrolysis per step: Myosin typically uses 11 ATP per power stroke.

Connections to Prior Lectures / Foundational Concepts

  • Builds on earlier discussion of cytoskeletal tracks (microtubules) and their motors (kinesin/dynein).

  • Reinforces theme: molecular machines use ATP to convert chemical to mechanical energy.

  • Demonstrates cellular division of labor—microtubules for long-range, actin for short-range/localized transport.

Real-World & Biomedical Relevance

  • Muscle Disorders: Mutations in myosin-II cause cardiomyopathies and skeletal myopathies.

  • Pigmentation: Myosin-Va mutations lead to Griscelli syndrome (defective melanosome transport).

  • Pathogen Exploitation: Some viruses hijack actin-myosin pathways to spread within host cells.

  • Drug Targets: Small-molecule inhibitors of myosin ATPase are under investigation for cancer metastasis and heart failure therapy.

Ethical / Philosophical Considerations

  • Manipulating motor proteins may cure disease but raises concerns about unintended impacts on development and neural function.

  • Synthetic biology: engineering artificial motors prompts discussion on limits of redesigning life’s fundamental machinery.

Key Terms & Definitions

  • Actin Microfilament: ∼7 nm\sim7\,\text{nm} diameter polymer of globular actin (G-actin) subunits.

  • Myosin Superfamily: Diverse group of actin-dependent ATPase motors.

  • ATPase: Enzyme that hydrolyzes ATP, releasing energy.

  • Power Stroke: Conformational change in motor protein that generates force.

  • Cargo: Any transported entity—vesicle, organelle, mRNA, protein complex, or membrane segment.