Figure 2. Overview of dynein composition.

a | Linear representation of domains within the dynein heavy chain. The amino-terminal tail domain is involved in dynein oligomerization, cargo-binding and regulation, but is not part of the minimal motor domain capable of producing movement in vitro. The motor domain comprises the linker domain, six AAA+ modules (1–6), the coiled-coil stalk and strut, and the carboxy-terminal region. The motor domain of Dictyostelium discoideum dynein has a molecular mass of ~380 kDa. In many fungal dyneins, the C-terminal region is shorter and the motor domain is ~330 kDa. Each of the AAA+ modules is composed of a large N-terminal subdomain and a smaller C-terminal subdomain (see inset and Box 2). b | The cytoplasmic dynein complex contains a pair of identical heavy chains. Within each heavy chain, the six AAA+ modules fold into a ring. The stalk protrudes as an extension from the small subdomain of AAA4. The tail is connected to AAA1 by the linker domain, which arches over the AAA+ ring. In Chlamydomonas reinhardtii inner arm dynein-c, a sharp ~90° kink exists between the linker and the tail^{90, 92, 115}. Although not yet visualized in cytoplasmic dynein, a similar kink might exist, as it would prevent a steric clash between the tail and the microtubule. In dynein-c, this neck region of the tail is a natural site of flexibility in the molecule, allowing the angle of the tail to vary with respect to the motor domain^{90, 92, 115}. The cytoplasmic dynein heavy chains assemble with up to five types of associated subunit, which are also dimers¹⁴⁸. The associated subunits comprise the intermediate chain, the light-intermediate chain and three classes of light chain: TCTEX, LC8 and Roadblock. Dashed lines indicate reported interactions of the associated subunits with each other and with the tail²⁶. The three-dimensional (3D) arrangement of the associated subunits with respect to the tail is unknown. c | A 3D model of the cytoplasmic dynein motor domain bound to the microtubule (the associated subunits are not shown). As no high-resolution structure currently exists for the entire motor domain bound to a tubulin dimer, this model is based on a 2.8 Å crystal structure of the D. discoideum dynein motor domain lacking the microtubule-binding domain⁹³ (Protein Data Bank ID: 3VKG), joined to a cryo-electron microscopy-derived model of the mouse microtubule-binding domain bound to an α-tubulin–β-tubulin dimer¹¹² (Protein Data Bank ID: 3J1T). Subdomains are shown in surface representation, with the two long α-helices in the stalk rendered separately to emphasize their coiled-coil arrangement. The six AAA+ modules are numerically labelled.