Kinesin proteins function as molecular couriers inside living cells, transporting a wide variety of packages to their intended destinations. These biological machines move along protein filaments called microtubules, which form a complex network of highways crisscrossing the cell’s interior. This transport system supports many cellular activities, from moving vesicles and organelles to ensuring chromosomes are correctly separated during cell division. The movement of kinesin is an active process, powered by the chemical energy stored in adenosine triphosphate (ATP), allowing them to carry cargo over significant distances.
Overall Architecture of Kinesin-1
The most well-studied member of this protein family, Kinesin-1, is a dimer, meaning it is constructed from two identical protein chains, known as heavy chains. This assembly gives the molecule a distinct, elongated shape that can be conceptually divided into three main functional regions.
At one end of the molecule are two globular structures called the motor heads. These domains are the active components of the machine, containing the machinery needed to bind to the microtubule highway and to harness energy. Following the heads is a long, central stalk formed by the two heavy chains twisting around each other into a stable structure known as a coiled-coil. The stalk acts as a rigid spacer, connecting the motor heads to the final domain.
At the opposite end from the motor heads lies the tail domain. This part of the protein is responsible for interacting with the cellular cargo that needs to be transported. The tail domain associates with additional proteins called light chains, which act as adaptors, allowing the kinesin to bind to a wide variety of different packages, from synaptic vesicles in a neuron to organelles like mitochondria.
The Motor Domain in Detail
The motor head contains a highly conserved catalytic core that serves as the engine for movement. This domain is responsible for both interacting with the microtubule and for converting chemical energy into mechanical force. Its structure contains a specialized pocket designed to bind and process ATP. The geometry of this pocket allows it to hold an ATP molecule and facilitate its hydrolysis—the chemical reaction that breaks it down into adenosine diphosphate (ADP) and a phosphate group.
The surface of the motor head that physically contacts the microtubule is known as the microtubule-binding interface. This interface is not static; its shape and chemical properties change depending on the state of the nucleotide-binding pocket. When ATP is bound, the interface has a high affinity for the microtubule, gripping it tightly. Following ATP hydrolysis to ADP, this affinity is significantly reduced, allowing the head to detach from its track.
Connecting the globular motor head to the long stalk is a short, flexible strand of the protein called the neck linker. This component is an active participant in generating force. The conformational state of the neck linker is directly controlled by the nucleotide bound in the motor head’s pocket.
Structural Basis of Movement
The movement of Kinesin-1 along a microtubule is a coordinated, stepwise process called a “hand-over-hand” mechanism. This walking motion is driven by a repeating cycle of chemical and structural changes powered by ATP hydrolysis. The process begins with one of the two motor heads, the lead head, firmly attached to the microtubule, while the other head, the trailing head, is detached and holds an ADP molecule.
The cycle is initiated when an ATP molecule binds to the attached lead head. This binding event triggers a conformational change within the head, which causes the flexible neck linker to dock into a rigid, forward-pointing orientation. This docking action is the power stroke of the motor; it swings the detached, ADP-bound trailing head forward over the stationary lead head.
The head is swung approximately 16 nanometers forward to the next available binding site on the microtubule. As this forward head binds, it releases its ADP molecule. This binding event sends a signal through the stalk to the other head, which is still bound to its original position and now holds ATP.
This signal stimulates the rear head to hydrolyze its bound ATP into ADP and a phosphate group. The hydrolysis event weakens the rear head’s grip on the microtubule, causing it to detach. With this detachment, the motor has completed a full step, and the roles of the two heads are now reversed so the cycle can begin again.
Structural Diversity Across the Kinesin Superfamily
While Kinesin-1 provides a classic example of a cargo transporter, it represents just one member of a large and functionally diverse superfamily of proteins. Structural adaptations, such as changes to the number and placement of motor domains, allow different kinesins to perform a wide range of specialized functions beyond simple transport.
An example of this diversity is Kinesin-5. Unlike the two-headed structure of Kinesin-1, Kinesin-5 proteins assemble into a bipolar tetramer, composed of four chains with motor domains at both ends of the complex. This arrangement prevents them from walking along a single microtubule. Instead, Kinesin-5 binds to two separate microtubules and slides them against each other, a function for pushing the poles of the mitotic spindle apart during cell division.
Another variation is found in Kinesin-13, where the motor domain is not located at the end of the protein chain but is situated in the middle. This central placement of the motor domain makes it incapable of processive walking. Instead, Kinesin-13 molecules bind to the ends of microtubules and use the energy from ATP hydrolysis to promote the removal of tubulin subunits, causing the disassembly of the microtubule track.