There are three classes of bi-pedaling transporters: cytoplasmic dynein and kinesins, which utilize a network of tubular filaments called microtubules for long-range transport, and myosins, which move along actin filaments.
Despite differences in size and structural makeup, dynein, the kinesins and the myosins share a number of defining features.
First, they assemble around two identical monomers, each of which consists of a "head" region responsible for filament track binding and for converting cellular energy in the form of ATP into mechanical work, and an extended "tail" region for head-head dimerization and cargo binding.
Second, each of the motors has acquired specialized structures for track binding, force amplification, and for ATP binding and hydrolysis.
Third, the motors share a mechanism for sustained stepping and forward movement that hinges on inter-head communication. To learn more, go to CHEMOMECHANICS and STEPPING.
Cytoplasmic dynein and its adapter dynactin (in black) serve in a wide range of cellular processes, including transport of vesicles, virus, signaling factors and large organelles.
The enormous size, structural complexity and large number of regulatory pathways set cytoplasmic dynein apart from the kinesins and myosins.
Dynein's ability to produce force and move along a microtubule evolves from and revolves around a large ring of six AAA domains, three of which are catalytically active. Nucleotide binding and hydrolysis at these sites set about conformational changes that are transmitted to three major structures: a force-amplifying domain, a slender microtubule binding element, and a C-terminal domain that acts as a potent force regulator.
The tail is responsible for head-head dimerization and for binding to a variety of dynein subunits and accessory proteins that serve in cargo recruitment, motor regulation and retention of dynein stability.
KINESIN-1, -2 AND -3
The kinesins consist of an extended family of 14 members, three of which are transporters: kinesin-1, -2 and -3. The kinesins and cytoplasmic dynein frequently bind to the same cellular cargo but move in opposite directions on a microtubule. Transport of cargo is thus subjected to a complex and ambiguous process of competition and cooperation.
The size of kinesin is only 1/10 of that of dynein but it masters to generate 6-times higher force. As a result, multiple dyneins are typically recruited to a cargo to counteract the force produced by a single kinesin.
The kinesin head is highly conserved and consists of archetypal nucleotide- and microtubule-binding sites, and a small mechanical element ("neck linker") that amplify conformational changes at the catalytic site into larger structural movements for force production.
In addition to having roles in homodimerization and cargo binding, the kinesin tail can in absence of bound cargo adopt a folded conformation that shuts off the motor and prevent it from engaging in futile work.
MYOSIN V AND VI
Myosin V and VI are actin-associated transporters that operate primarily at the actin-rich periphery of the cell where they are implicated in endocytosis and vesicular trafficking.
As an adoption to the geometry of the actin filament, the myosins have evolved extraordinary long "neck" regions, which serve in torque generation, and in binding multiple copies of a calcium binding structure involved in neck stabilization and motor regulation. Myosin VI binds two of these structures (see left) while the longer neck of myosin V binds six.
The overall design of the myosin head is similar to that of cytoplasmic dynein and the kinesins, having structures for nucleotide- and filament-binding, and for regulation of nucleotide accessibility at the catalytic site.
Alike the kinesins, the myosin tail can adopt a bend conformation that inactivates the motor in absence of bound cargo.