Roles of microtubules and LIS1 in dynein transport machinery assembly
Article metadata
Article Date: 18 February 2026
Article URL: https://www.nature.com/articles/s41586-026-10153-y
Article Image: (no central image provided)
Summary
This Nature study uses extensive cryo-EM, biochemical assays and mass photometry to map how microtubules and the regulator LIS1 shape assembly of dynein transport complexes. The authors report multiple cryo-EM reconstructions of dynein, dynein–dynactin and dynein–dynactin–adaptor complexes bound to microtubules (DD–MT, D–MT and several adaptor-containing states) and show how microtubule binding and LIS1 modulate adaptor recruitment, complex stability and dynein conformations.
Key Points
- Cryo-EM structures and maps for many dynein/dynactin/adaptor states bound to microtubules have been deposited (multiple PDB/EMDB entries).
- Microtubules act as a scaffold that promotes formation of dynein–dynactin (DD) complexes on the lattice and influence adaptor entry into a dynamic adaptor-binding groove.
- LIS1 associates with DD–MT to form DDL–MT assemblies and shifts dynein conformational distributions, implicating LIS1 in promoting activated complex formation on MTs.
- Adaptor identity and the dynamic state of the adaptor-binding groove control recruitment and competition between adaptors (examples: BicdR1, Trak2, HOOK3).
- Nucleotide state affects DD binding to microtubules — biochemical pelleting assays show different affinities in Apo/ADP/AMPPNP/ATP/ADP·Vi states.
- Adaptor competition and deletion-construct experiments define essential adaptor motifs (DLIC-binding motif, CC1/IH regions) needed for recruitment and displacement behaviour.
- Analysis pipelines and code for cryo-EM processing used in the study are available on GitHub to reproduce multi-curve fitting and tubulin-lattice subtraction steps.
Content summary
The authors combined microtubule co-sedimentation, negative-stain EM, mass photometry and high-resolution cryo-EM to capture a series of dynein-containing assemblies on microtubules. They characterised a DD–MT complex (dynein bound with dynactin on the MT lattice), single dynein motor domain arrangements (D–MT) and multiple adaptor-bound states (DDR, DDK, DDL and variations with LIS1).
Structural classification revealed a dynamic adaptor-binding groove on the dynein tail that ranges from tight to loose conformations; this groove regulates how adaptors enter and stabilise the dynein–dynactin assembly. Biochemical pelleting and competition assays showed that adaptors can displace one another from pre-assembled complexes depending on their binding motifs, and that LIS1 association stabilises specific assemblies (DDL–MT) and alters dynein conformational populations. The work also documents nucleotide-dependent differences in DD–MT binding and provides extensive supplementary and extended-data figures with validation, processing workflows and methodological details.
Context and relevance
This paper sits at the intersection of structural biology and intracellular transport regulation. It refines our mechanistic understanding of how the microtubule lattice and LIS1 cooperate to assemble activated dynein complexes in situ, rather than viewing activation as solely an off-MT biochemical event. The findings matter for anyone studying cargo transport, neuronal migration (LIS1 is linked to lissencephaly), adaptor specificity, or the regulation of motor activity by lattice interactions.
Practically, the study provides a set of cryo-EM maps and processing code that other groups can reuse to probe large microtubule‑based motors, and it clarifies how adaptor choice and nucleotide state tune dynein recruitment — important for interpreting in vitro reconstitutions and cellular imaging data.
Why should I read this?
Short and blunt — if you work on dynein, LIS1 or intracellular transport, this is proper essential reading. It bundles high‑res structures, biochemical assays and reusable code to explain how MT binding and LIS1 help build the active transport machine. If you don’t have time, read the Key Points and the Source link below — we’ve saved you the heavy lifting.
Author note
Punchy take: the team provides concrete structural snapshots and complementary assays that push forward how we think dynein is assembled and primed for transport on microtubules. For specialists, the deposited maps and code are high value; for broader cell biology readers, the LIS1–MT interplay gives a clear mechanistic hook linking molecular structure to cellular roles.