13.1 Structure and function of molecular motors

Molecular motors are protein powerhouses that convert chemical energy into mechanical work. These tiny machines drive essential cellular processes, from muscle contraction to cell division, by harnessing the power of ATP hydrolysis.

The structure of molecular motors is key to their function. Motor domains, neck linkers, and cargo-binding regions work together to generate force and motion. Understanding these components helps us grasp how cells move, transport cargo, and maintain their internal organization.

Molecular motor components and function

Motor domain and ATP hydrolysis

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• Molecular motors are protein complexes that convert chemical energy, typically from ATP hydrolysis, into mechanical work for various cellular processes
• The motor domain is the catalytic core of molecular motors, responsible for ATP binding and hydrolysis
  • Contains the nucleotide-binding site and the active site for catalysis
  • ATP binding and hydrolysis in the motor domain drive conformational changes that generate force and motion

Neck linker and lever arm

• The neck linker is a flexible region adjacent to the motor domain that undergoes conformational changes during the mechanochemical cycle
  • Contributes to the generation of force and motion by amplifying the conformational changes in the motor domain
• Some molecular motors, such as myosin, have a lever arm that amplifies the small conformational changes in the motor domain
  • Lever arm enables larger displacements and increased force generation

Stalk or tail domain and cargo interactions

• The stalk or tail domain of molecular motors interacts with cytoskeletal filaments (microtubules or actin) and cargo
  • Enables the motor to move along the filaments or transport cargo to specific locations within the cell
• The structure of the stalk or tail domain determines the motor's specificity for certain cytoskeletal filaments and cargo
  • Allows for targeted transport and localization within the cell

Classifying molecular motors

Cytoskeletal motors

• Cytoskeletal motors are molecular motors that interact with cytoskeletal filaments
  • Include myosin (interacts with actin filaments), kinesin, and dynein (interact with microtubules)
• Myosin motors are involved in muscle contraction, cell migration, and intracellular transport
  • Move along actin filaments and generate contractile forces
• Kinesin motors typically move towards the plus end of microtubules
  • Involved in intracellular transport of organelles, vesicles, and other cellular components
• Dynein motors move towards the minus end of microtubules
  • Involved in intracellular transport, cell division, and cilia and flagella movement

Rotary and nucleic acid motors

• Rotary motors, such as F0F1-ATP synthase and the bacterial flagellar motor, convert chemical energy into rotational motion
  • F0F1-ATP synthase uses proton gradient for ATP synthesis
  • Bacterial flagellar motor drives bacterial locomotion
• Nucleic acid motors, such as DNA and RNA polymerases, helicases, and topoisomerases, are involved in DNA and RNA metabolism
  • DNA and RNA polymerases catalyze the synthesis of DNA and RNA
  • Helicases unwind double-stranded nucleic acids during replication and transcription
  • Topoisomerases regulate DNA topology by introducing or removing supercoils

Force generation in molecular motors

Mechanochemical cycle and conformational changes

• The mechanochemical cycle of molecular motors involves the coupling of ATP hydrolysis with conformational changes in the motor domain
  • Results in force generation and motion along the cytoskeletal filament
• ATP binding to the motor domain induces a conformational change that increases the affinity of the motor for its cytoskeletal filament
  • Leads to a strong binding state between the motor and the filament
• ATP hydrolysis and the release of inorganic phosphate (Pi) cause a conformational change in the neck linker or lever arm
  • Generates a power stroke that displaces the motor along the filament

Coordination of multiple motor domains

• The coordination of multiple motor domains within a single motor complex enables processive movement along the filament
  • Dimeric kinesin or myosin motors maintain continuous contact with the filament through alternating cycles of ATP hydrolysis and binding
• The collective action of multiple motors working together can generate larger forces and more complex movements
  • Muscle contraction results from the coordinated action of multiple myosin motors
  • Cilia and flagella beating is driven by the synchronized activity of dynein motors

Structure-function relationship of molecular motors

Structural features and their functional implications

• The specific structural features of molecular motors enable them to perform their specialized functions in different biological processes
• The size and shape of the motor domain determine the type of nucleotide (ATP or GTP) that can bind and the rate of hydrolysis
  • Affects the motor's speed and processivity
• The length and flexibility of the neck linker or lever arm influence the step size and the amount of force generated by the motor
  • Longer and more rigid lever arms enable larger displacements and higher force generation
• Variations in the arrangement and number of motor domains within a motor complex contribute to differences in processivity, speed, and force generation
  • Multiple heads in dynein or the formation of dimers or tetramers in kinesin and myosin enhance processivity and force output

Regulation and coordination of molecular motors

• Post-translational modifications, such as phosphorylation or acetylation, can modulate the activity and regulation of molecular motors
  • Allows motors to respond to cellular signals and adapt to different physiological conditions
• The coordinated action of different types of molecular motors is essential for complex biological processes
  • Cell division requires kinesins and dyneins to assemble and position the mitotic spindle, while myosins contribute to cytokinesis
  • Intracellular transport involves the cooperation of kinesins and dyneins to move cargo bidirectionally along microtubules