#motor protein

Cytoskeleton

Which component of dynein is primarily responsible for generating movement?

Generation of force in dynein occurs in motor domain comprising six AAA+ modules organized in a closed ring with large linker arching over it. AAA1 through AAA4 can bind nucleotide, but only AAA1 and AAA3 hydrolyze productively to drive movement. In ATP-bound state AAA1-AAA2 closure pulls AAA2 away from AAA3, propagating conformational change through AAA4-AAA6 to stalk coiled-coil, shifting registry and lowering affinity for microtubule. Subsequent phosphate release closes ring further, driving linker domain rotation of approximately eight nanometers from straight to bent conformation docked at AAA2. This lever arm motion moves N-terminal tail attached to dynactin and cargo toward minus end. Cryo-electron microscopy of different nucleotide states reveals stalk helix sliding and buttress-mediated coordination. Isolated stalk fragments bind microtubules without motion, stem holds dimerization, cargo-binding domain selects adaptors, confirming motor ring as energy transducing engine converting chemical energy of ATP hydrolysis into mechanical displacement. Integration with cell cycle kinases, calcium signaling and mechanical cues ensures coordinated remodeling during growth, migration and differentiation.

Ref: Carter Nature 2011; AAA+ ring AAA1 hydrolyzes ATP driving linker swing, motor core force.

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Cytoskeleton

Which motor protein moves cilia and flagella?

Cilia and flagella motility requires active sliding filament machine within conserved axoneme evolutionary ancient. Structure nine outer doublet microtubules surrounding central pair retains dynein motors as exclusive driver of beating: outer dynein arms contain two or three heavy chains per arm inner arms more heterogeneous but also axonemal dynein isoforms both anchored to A tubule via docking complex and reaching to B tubule of neighboring doublet executing ATP hydrolysis cycle. Power stroke toward minus end attempts to slide doublets relative each other but nexin dynein regulatory complex NDRC and radial spokes constrain sliding converting linear force into bending moment propagated along length in oscillatory fashion regulated by calcium calmodulin kinases and central pair rotation. Kinesin-1 transports mitochondria outward on cytoplasmic microtubules also drives anterograde intraflagellar transport constructing flagellum but not bending itself Myosin II actin based contractility not involved in axonemal bending. Hence dynein powers motion with coordinated activation producing wave form for mucus propulsion sperm swimming and left right patterning nodal flow.

Ref: King, J Cell Sci 2012 – Dynein motor protein moves cilia and flagella beating machinery.

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Cytoskeleton

Which motor protein powers ciliary and flagellar movement?

Motile cilia and flagella beating powered exclusively by axonemal dynein distinct isoforms from cytoplasmic dynein-1 adapted for high duty cycle sliding. Outer and inner dynein arms attached every 24 and 96 nm along A tubule heavy chains contain AAA ring and microtubule binding stalk pointing toward adjacent B tubule executing ATP hydrolysis cycle. Cycle drives linker bending delivering power stroke causing interdoublet sliding about 5 microns per second in disintegrated axoneme. In intact cilia doublets anchored at basal body and crosslinked by nexin dynein regulatory complex forces converted into bending propagating wave. Kinases phosphatases regulate dynein via central pair radial spoke signaling pathway orchestrating oscillatory activity switching sides. Kinesin-1 drives anterograde intraflagellar transport constructing flagellum not beating myosin systems unrelated operating on actin stathmin sequesters tubulin dimer. Therefore dynein provides motive force for ciliary clearance mucus propulsion and sperm propulsion defects cause Kartagener syndrome primary ciliary dyskinesia with situs inversus. Additional regulatory inputs including phosphorylation, small GTPases, and cargo adaptors fine tune filament assembly stability and motor activity matching cellular demands during division, migration, and mechanical stress responses efficiently.

Ref: Viswanadha et al., Biosci Rep 2017 – Dynein powers ciliary and flagellar movement via axonemal arms.

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Cytoskeleton

Kinesin-13 differs from other kinesins because it:

Kinesin superfamily generally couples ATP hydrolysis to processive stepping for cargo transport using hand over hand mechanism but kinesin-13 family including mitotic centromere associated kinesin MCAK KIF2C and KIF2A exhibits depolymerase activity instead of transport. These kinesins possess central motor domain flanked by N and C termini diffuse along microtubule lattice without directional ATP dependent stepping and concentrate at ends via one dimensional diffusion to both tips. At tip they stabilize curved protofilament conformation accelerating removal of tubulin subunits and inducing catastrophe by bending protofilaments outward. Hydrolysis not used for walking but for detaching tubulin and recycling itself after removal. Functionally they regulate spindle length correct erroneous kinetochore attachments by depolymerizing misattached microtubules and tune dynamic instability threshold. Thus kinesin-13 enhances microtubule depolymerization rather than forming filaments or crosslinking actin defining distinct mechanistic class within kinesins important for mitotic fidelity. Additional regulatory inputs including phosphorylation, small GTPases, and cargo adaptors fine tune filament assembly stability and motor activity matching cellular demands during division, migration, and mechanical stress responses efficiently.

Ref: Walczak et al., Annu Rev Cell Dev Biol – Kinesin-13 depolymerase activity mechanism classification.

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Cytoskeleton

What is the primary function of dynein in cellular transport?

Cellular cargo movement includes vesicular trafficking but cilia and flagella beating demands distinct high power motors specialized for sliding instead of cargo carrying. Axonemal dynein evolved from cytoplasmic dynein forms large arrays of outer and inner dynein arms repeating every 96 nm along A tubule of axonemal doublet in nine fold symmetric axoneme. Each arm hydrolyzes ATP in AAA1 to AAA4 rings transmitting conformational change through stalk causing sliding of adjacent B tubule toward base at velocities up to 5 microns per second. Because axoneme constrained by radial spokes linking doublets to central pair and nexin dynein regulatory complex crosslinking doublets sliding converted into bending propagated as waves driving fluid propulsion. Cytoplasmic dynein transports vesicles toward minus ends transport toward plus ends performed by kinesin severing done by katanin. Thus major force for cilia and flagella movement originates from axonemal dynein essential for mucociliary clearance reproduction and left right asymmetry establishment during development.

Ref: Ishikawa, Curr Biol – Dynein generates force for cilia flagella movement via axonemal arms.

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Cytoskeleton

Which motor protein moves cargo towards the (+) end of microtubules?

Long distance intracellular transport along microtubules employs directional motors whose motor domains read polarity via asymmetric binding and neck linker orientation. Majority of kinesin superfamily members possess N terminal motor domains that exhibit plus end directed motility via neck linker docking mechanism: ATP binding induces neck linker zippering toward plus end swinging trailing head forward 8 nm. Kinesin-1 KIF5B exemplifies conventional plus motor ferrying mitochondria synaptic vesicle precursors lysosomes and mRNP anterogradely toward cell periphery or axon terminals at about 1 micron per second. Dynein is obligate minus end directed motor moving cargo toward centrosome and nucleus for degradation. Myosin II operates on actin filaments for contractility not microtubules. Kinesin-14 family such as NCD and HSET moves minus end due to C terminal motor domain inverted orientation. Hence kinesin-1 epitomizes plus end cargo transport underlying polarized distribution peripheral positioning and axonal anterograde traffic essential for synaptic function and organelle inheritance during division.

Ref: Vale, Cell 2003 – Kinesin family plus end motility; Alberts Chapter 16 Kinesin-1 transport role.

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Cytoskeleton

Actin filaments interact with which motor protein for intracellular transport?

Two distinct superfamilies of cytoskeletal motors evolved to walk along filaments using ATP hydrolysis. Myosin motors share N terminal head motor domain containing actin binding interface including helix turn helix, cardiomyopathy loop, P loop ATPase, Switch I II for gamma phosphate sensing and lever arm with IQ motifs binding calmodulin light chains. Upon interaction with F actin 7 nanometer helical filament, head undergoes conformational cycle releasing phosphate driving swing of lever arm producing force along filament. Diverse isoforms specialize: myosin II non processive forming bipolar filaments for contraction, myosin V processive dimer for cargo, myosin I single headed tension sensor. In contrast dynein heavy chain AAA plus ring and coiled coil stalk binds microtubule 25 nanometer tubule, kinesin motor domain with tubulin binding loops moves along protofilaments. Nexin is non motor linker between doublet microtubules in axoneme. Therefore actin filament based intracellular transport and contractility specifically require myosin family as dedicated actin associated motor providing directional movement.

Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 16: Myosin Motors and Actin Filaments.

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