Kinesins and Dyneins

Core Concept

Microtubule motor proteins are ATPases that convert the energy of ATP hydrolysis into directed movement along the microtubule lattice. They belong to two superfamilies: kinesins, most of which move toward the plus end, and dyneins, which (with one ciliary exception) move toward the minus end. This polarity division organizes the cell: kinesins carry cargo outward (e.g., toward the axon terminal or cell periphery), while cytoplasmic dynein carries cargo inward (toward the cell center, near the centrosome). Both motors are dimers that "walk" processively, but they are built on entirely different structural principles.

Key Components

• Kinesin-1 (conventional kinesin): a tetramer of two heavy chains and two light chains. Each heavy chain has a globular motor head (ATPase + microtubule-binding), a neck linker, a long coiled-coil stalk, and a tail that binds cargo (often via light chains/adaptors).
• Kinesin families: kinesin-1 (organelle transport), kinesin-2 (intraflagellar transport), kinesin-5 (spindle, Eg5), kinesin-13/MCAK (a depolymerizer, not a walker), and kinesin-14 (minus-end-directed, e.g., Ncd).
• Cytoplasmic dynein: a massive (~1.5 MDa) complex; the heavy chain contains a ring of six AAA+ ATPase domains, a linker, and a long stalk ending in the microtubule-binding domain. Associated intermediate, light-intermediate, and light chains provide cargo attachment.
• Dynactin: a large accessory complex required for most cytoplasmic dynein functions; together with coiled-coil adaptors (BICD2, Hook, RAB11-FIP3), it activates and links dynein to cargo.
• Processivity: the ability to take many steps without dissociating.

Mechanism / How It Works

1. A kinesin dimer binds the microtubule with one head; ATP binding to the leading head triggers its neck linker to "dock," which throws the trailing head forward.
2. The trailing head lands 8 nm ahead (one tubulin dimer), binds the next site, and releases its ADP — a hand-over-hand walk toward the plus end.
3. ATP hydrolysis (on the newly bound head) resets the cycle; because each step consumes one ATP, the motor advances 8 nm per ATP.
4. The two heads alternate binding so at least one is always attached, making kinesin-1 highly processive (hundreds of steps before falling off).
5. Cytoplasmic dynein moves by a different mechanism: ATP hydrolysis in its AAA+ ring drives the linker to swing (a power stroke), while the stalk's affinity for the microtubule cycles between strong (ATP) and weak (ADP·Pᵢ) — a minus-end-directed walk. Dynein's stepping is more variable and requires dynactin + adaptor for processive, cargo-bound movement.
6. Polarity is intrinsic: kinesin and dynein read the α/β lattice orientation, so each motor type moves in only one direction.

Energy and Directionality

Both motors are ATPases (unlike the GTP-driven assembly of tubulin). Each kinesin step consumes one ATP; each dynein power stroke likewise couples ATP hydrolysis in the AAA+ ring. Directionality is a structural property of the motor domain: most kinesins are plus-end-directed (except kinesin-14), and cytoplasmic dynein is minus-end-directed. The cell exploits this fixed polarity to create bidirectional traffic — kinesins deliver, dynein retrieves — along the same oriented tracks.

Experimental Evidence / Technique

• In vitro motility (gliding) assays: purified motors attached to a coverslip translocate microtubules; direction and velocity (kinesin ~0.8 µm/s) are measured by video microscopy.
• Single-molecule optical tweezers / fluorescence: kinesin's 8 nm steps and processive runs were measured directly, confirming hand-over-hand stepping.
• ATP analog and kinetic studies: non-hydrolyzable analogs (AMPPNP) trap kinesin on the microtubule; pre-steady-state kinetics map the ATPase cycle to stepping.
• Function-blocking antibodies / RNAi: blocking kinesin or dynein/dynactin redistributes organelles, proving their opposite transport roles in vivo.
• Axonal transport imaging: live tracking of vesicles labeled with fluorescent cargo shows plus-end (kinesin) vs. minus-end (dynein) movement along axons.

How it works

1. A kinesin dimer binds the microtubule with one head; ATP binding to the leading head triggers its neck linker to "dock," which throws the trailing head forward.
2. The trailing head lands 8 nm ahead (one tubulin dimer), binds the next site, and releases its ADP — a hand-over-hand walk toward the plus end.
3. ATP hydrolysis (on the newly bound head) resets the cycle; because each step consumes one ATP, the motor advances 8 nm per ATP.
4. The two heads alternate binding so at least one is always attached, making kinesin-1 highly processive (hundreds of steps before falling off).
5. Cytoplasmic dynein moves by a different mechanism: ATP hydrolysis in its AAA+ ring drives the linker to swing (a power stroke), while the stalk's affinity for the microtubule cycles between strong (ATP) and weak (ADP·Pᵢ) — a minus-end-directed walk. Dynein's stepping is more variable and requires dynactin + adaptor for processive, cargo-bound movement.
6. Polarity is intrinsic: kinesin and dynein read the α/β lattice orientation, so each motor type moves in only one direction.

Common confusions

• "All kinesins move to the plus end." — Most do, but kinesin-14 (Ncd) is minus-end-directed, and kinesin-13 doesn't walk at all.
• "Kinesin and dynein use GTP." — No. They are ATPases; GTP is the nucleotide for tubulin assembly.
• "Dynein is just a bigger kinesin." — They are structurally unrelated: dynein's motor is an AAA+ ring with a stalk, not a kinesin-like head.
• "Myosin also walks on microtubules." — No. Myosin walks on actin filaments; kinesin and dynein walk on microtubules.
• "A single motor can go both directions." — Directionality is fixed per motor type; reversing cargo direction requires switching the motor (or regulation), not reversing one motor.

Quick review

• Kinesin = plus-end, ATP-driven, hand-over-hand, 8 nm steps; dynein = minus-end, AAA+ ring, needs dynactin.
• One ATP per kinesin step; processive because one head is always bound.
• Kinesin-1/2/5/13/14 differ in cargo and direction; kinesin-13 depolymerizes.
• Opposite polarity (kinesin vs. dynein) creates bidirectional transport on the same tracks.
• Defects → spastic paraplegia, motor neuron disease, ciliary dyskinesia; Eg5 is a drug target.
• Demonstrated by gliding assays, optical tweezers, and single-molecule imaging.