13.1 Structure and function of molecular motors
4 min read•august 1, 2024
Molecular motors are protein powerhouses that convert into mechanical work. These tiny machines drive essential cellular processes, from to , by harnessing the power of .
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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How molecular motors work – insights from the molecular machinist's toolbox: the Nobel prize in ... View original
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- Molecular motors are protein complexes that convert chemical energy, typically from hydrolysis, into mechanical work for various cellular processes
- The 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 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 , 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 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), , and (interact with microtubules)
- Myosin motors are involved in muscle contraction, cell migration, and
- 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
- The length and flexibility of the neck linker or lever arm influence the 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 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
Key Terms to Review (21)
ATP: Adenosine triphosphate (ATP) is the primary energy carrier in all living organisms, often referred to as the 'energy currency' of cells. It stores and transports chemical energy within cells, facilitating various biological processes, including metabolism, muscle contraction, and active transport. The conversion of ATP to ADP (adenosine diphosphate) releases energy that can be harnessed for cellular activities, making it essential for life.
ATP Hydrolysis: ATP hydrolysis is the chemical reaction where adenosine triphosphate (ATP) is broken down into adenosine diphosphate (ADP) and an inorganic phosphate (Pi), releasing energy that can be used for various biological processes. This reaction is crucial for understanding how energy is transferred in biological systems, particularly in the context of free energy changes and the movement of molecular motors.
Calcium signaling: Calcium signaling is a cellular communication mechanism where changes in intracellular calcium ion concentration act as a signal to trigger various physiological responses. This process is essential for many cellular activities, including muscle contraction, neurotransmitter release, and the regulation of gene expression, making it a fundamental aspect of cellular function and intercellular communication.
Cargo binding: Cargo binding refers to the specific interaction between a molecular motor and the cargo it transports, which can include various cellular components such as organelles, proteins, or vesicles. This interaction is crucial for ensuring that the cargo is correctly picked up and delivered to its intended destination within the cell. Cargo binding is influenced by the motor's structure, the type of cargo, and the cellular environment, making it a vital aspect of intracellular transport.
Cell division: Cell division is the process by which a parent cell divides into two or more daughter cells, ensuring the propagation of genetic material and cellular function. This fundamental biological process is essential for growth, repair, and reproduction in living organisms, and involves intricate mechanisms that are often facilitated by molecular motors. These motors play critical roles in moving chromosomes and organelles, ultimately enabling accurate and efficient division.
Chemical Energy: Chemical energy is the potential energy stored in the chemical bonds of molecules, which can be released or absorbed during a chemical reaction. This form of energy is crucial for various biological processes, as it fuels cellular activities and powers molecular motors that perform work within living organisms.
Conformational Changes: Conformational changes refer to the alterations in the three-dimensional shape of a molecule, often as a response to environmental factors or interactions with other molecules. These changes can significantly impact the functionality of biomolecules, affecting processes such as enzyme activity, molecular recognition, and motor protein movement. Understanding these changes is crucial for insights into molecular dynamics and mechanisms underlying biological functions.
Dynein: Dynein is a motor protein that plays a crucial role in cellular transport and movement by converting chemical energy derived from ATP hydrolysis into mechanical work. This large, complex protein is responsible for retrograde transport along microtubules, moving cellular components toward the minus end of the microtubule, which is typically oriented toward the cell center. Dynein's unique structure and function make it an essential player in various cellular processes, such as organelle positioning, mitosis, and ciliary movement.
Electron microscopy: Electron microscopy is a powerful imaging technique that uses electrons instead of light to visualize the fine details of samples at a much higher resolution than traditional light microscopy. This method allows researchers to observe the ultrastructure of biological samples, such as cells and tissues, and gain insights into their molecular organization and function. It provides detailed images that help in understanding complex systems like molecular motors and lipid bilayers.
Intracellular transport: Intracellular transport refers to the mechanisms and processes that facilitate the movement of substances within a cell. This transport is essential for distributing proteins, organelles, and other molecules to their proper locations, ensuring that cellular functions are carried out efficiently. The process relies heavily on molecular motors, which use energy derived from ATP hydrolysis to move cargo along cytoskeletal filaments.
Kinesin: Kinesin is a type of molecular motor protein that transports cellular cargo along microtubules, which are part of the cytoskeleton. It plays a critical role in various cellular processes by converting chemical energy derived from ATP hydrolysis into mechanical work, facilitating movement within cells. Kinesin's structure is adapted for its function, featuring a motor domain that interacts with microtubules and cargo-binding domains that ensure the efficient transport of various cellular components.
Microtubule binding: Microtubule binding refers to the interaction between proteins, particularly molecular motors, and the microtubules of the cytoskeleton. This process is essential for cellular transport and movement, enabling molecular motors like kinesin and dynein to travel along microtubules, facilitating the movement of organelles, vesicles, and other cargo within cells.
Motor domain: The motor domain refers to a specific region within molecular motors that is responsible for the movement and translocation of cargo along cellular structures like microtubules or actin filaments. This domain plays a critical role in converting chemical energy, typically derived from ATP hydrolysis, into mechanical work, facilitating essential processes like muscle contraction, intracellular transport, and cell motility.
Muscle contraction: Muscle contraction is the process by which muscle fibers generate force and shorten, enabling movement of the body or its parts. This process relies on ATP as the energy source, ion channels for electrical signaling, and molecular motors like myosin to facilitate the sliding filament mechanism that causes muscle fibers to contract.
Myosin: Myosin is a motor protein that plays a key role in muscle contraction and cellular movement by converting chemical energy from ATP hydrolysis into mechanical work. It interacts with actin filaments to facilitate movement within cells and is essential for various cellular processes, linking its function to the structure and dynamics of molecular motors, mechanochemical coupling, and the behavior of single molecules.
Phosphorylation: Phosphorylation is the process of adding a phosphate group (PO4) to a molecule, typically a protein, which can alter the molecule's function, activity, or location within a cell. This modification is crucial for various cellular processes, including energy transfer and signaling pathways. It is commonly associated with ATP, the main energy currency in cells, and plays a key role in the functioning of molecular motors that facilitate movement within cells.
Processivity: Processivity refers to the ability of a molecular motor, such as a protein that moves along a filament, to catalyze multiple reactions or perform multiple cycles of movement without detaching from its substrate. This characteristic allows molecular motors to efficiently transport cargo within cells or generate force for cellular movements, playing a vital role in various biological processes.
Single-molecule fluorescence: Single-molecule fluorescence is a powerful technique used to study individual molecules by detecting their emitted light when excited by a specific wavelength. This method allows scientists to gain insights into molecular interactions, conformational changes, and dynamics at the single-molecule level, providing a more detailed understanding of biological processes and molecular functions.
Stalk region: The stalk region is a structural component of certain molecular motors, such as kinesins and dyneins, that connects the motor domain to the cargo-binding domain. This flexible segment plays a crucial role in enabling movement and function by allowing the motor to adapt its conformation during the transport process along cytoskeletal filaments.
Step size: Step size refers to the distance a molecular motor moves in a single discrete action or cycle. This movement is crucial for the function of molecular motors, as it dictates how effectively they can transport cellular cargo or generate force. The step size is typically measured in nanometers and can vary between different types of molecular motors, influencing their efficiency and function within biological systems.
Tail domain: The tail domain is a specific structural component of molecular motors, often found at the end of the protein's structure. This domain plays a crucial role in determining the motor's interactions with other cellular components and can influence its cargo-binding capabilities. The tail domain contributes to the overall functionality of molecular motors by allowing them to transport various cellular materials along cytoskeletal tracks.