Cryo-electron microscopy and biochemical reconstitution analysis reveals that Nde1 enhances Lis1 binding to autoinhibited dynein, promoting formation of a Phi-like–Lis1 intermediate during dynein acti...

The cellular distribution of mitochondria in response to stress and local energy needs is governed by the relative activities of the microtubule-based molecular motors kinesin and dynein. The mechanis...

The cellular distribution of mitochondria in response to stress and local energy needs is governed by the relative activities of the microtubule-based molecular motors kinesin and dynein. The mechanis...

Cytoplasmic dynein-1, a microtubule (MT)-based motor protein, requires dynactin and a coiled-coil adaptor to form the processive dynein–dynactin–adaptor (DDA) complex1,2. The roles of MTs and dynein regulator lissencephaly-1 (LIS1) in DDA assembly have remained elusive. Here we use cryo-electron microscopy to determine the structural basis of MT- and LIS1-mediated DDA assembly. We show that an adaptor-independent dynein–dynactin complex spontaneously forms on MTs with an intrinsic 2:1 stoichiometry in a highly efficient manner, driven by parallel alignment of dynein tails upon MT binding. Adaptors can wedge into and exchange within the assembled MT-bound dynein–dynactin complex; these processes are enabled by relative rotations between dynein and dynactin and facilitated by the dynein light-intermediate chains that assist the adaptor ‘search’ mechanism. Although LIS1 is dispensable for efficient DD(A)–MT assembly, its presence expands the conformational landscape of DD(A) assemblies on

Cryo-electron microscopy suggests a model in which microtubules, rather than adaptors in the cytoplasm, act as the primary platform for dynein–dynactin assembly, while LIS1 stabilizes low-microtubule-affinity intermediates near the pre-assembled complexes.

Chai et al. use cryo-electron microscopy to systematically interrogate the conformational landscape of motor protein dynein. The reported structures reveal intermediate states in the mechanochemical c...

NuMA activates dynein to organize the mitotic spindle by linking motor-driven transport with microtubule (MT) minus-end control. Mitotic phosphorylation relieves NuMA autoinhibition, enabling dynein m...

TIRF imaging of CRISPR-edited human cells shows dynein–dynactin complexes move processively with motility parameters consistent with the presence of multi-dynein assemblies (>one dynein heavy chain...

Dynein–dynactin–cargo adaptor complexes typically function with two dynein motors. Rao et al. show that, under mechanical load, these complexes can recruit a third dynein via a second adaptor, increas...

imageimageDynein-2 is a motor protein essential for retrograde intraflagellar transport (IFT) on the A-tubule of ciliary doublet microtubules. Here, biochemical and cryo-ET analyses demonstrate that d...