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Cryo-EM reveals the complex architecture of dynactin's shoulder region and pointed end.

Figure 1
<div class='caption-title'>Data processing pipeline for high‐resolution dynactin maps</div>
Figure 2
Lau CK, O'Reilly FJ, Santhanam B, Lacey SE, Rappsilber J, Carter AP
OpenAccess logo EMBO J 40 e106164 (2021)
Related entries: 6znl, 6znm, 6znn, 6zno

Cited: 12 times
EuropePMC logo PMID: 33734450

Abstract

Dynactin is a 1.1 MDa complex that activates the molecular motor dynein for ultra-processive transport along microtubules. In order to do this, it forms a tripartite complex with dynein and a coiled-coil adaptor. Dynactin consists of an actin-related filament whose length is defined by its flexible shoulder domain. Despite previous cryo-EM structures, the molecular architecture of the shoulder and pointed end of the filament is still poorly understood due to the lack of high-resolution information in these regions. Here we combine multiple cryo-EM datasets and define precise masking strategies for particle signal subtraction and 3D classification. This overcomes domain flexibility and results in high-resolution maps into which we can build the shoulder and pointed end. The unique architecture of the shoulder securely houses the p150 subunit and positions the four identical p50 subunits in different conformations to bind dynactin's filament. The pointed end map allows us to build the first structure of p62 and reveals the molecular basis for cargo adaptor binding to different sites at the pointed end.

Reviews citing this publication (3)

  1. Cargo-Mediated Activation of Cytoplasmic Dynein in vivo. Xiang X, Qiu R. Front Cell Dev Biol 8 598952 (2020)
  2. Multiple roles for the cytoskeleton in ALS. Liu X, Henty-Ridilla JL. Exp Neurol 355 114143 (2022)
  3. The PDLIM family of actin-associated proteins and their emerging role in membrane trafficking. Healy MD, Collins BM. Biochem Soc Trans 51 2005-2016 (2023)

Articles citing this publication (9)

  1. Sequential dynein effectors regulate axonal autophagosome motility in a maturation-dependent pathway. Cason SE, Carman PJ, Van Duyne C, Goldsmith J, Dominguez R, Holzbaur ELF. J Cell Biol 220 e202010179 (2021)
  2. Structure of dynein-dynactin on microtubules shows tandem adaptor binding. Chaaban S, Carter AP. Nature 610 212-216 (2022)
  3. Conserved roles for the dynein intermediate chain and Ndel1 in assembly and activation of dynein. Okada K, Iyer BR, Lammers LG, Gutierrez PA, Li W, Markus SM, McKenney RJ. Nat Commun 14 5833 (2023)
  4. Conformational transitions of the Spindly adaptor underlie its interaction with Dynein and Dynactin. d'Amico EA, Ud Din Ahmad M, Cmentowski V, Girbig M, Müller F, Wohlgemuth S, Brockmeyer A, Maffini S, Janning P, Vetter IR, Carter AP, Perrakis A, Musacchio A. J Cell Biol 221 e202206131 (2022)
  5. Antiviral function and viral antagonism of the rapidly evolving dynein activating adaptor NINL. Stevens DA, Beierschmitt C, Mahesula S, Corley MR, Salogiannis J, Tsu BV, Cao B, Ryan AP, Hakozawki H, Reck-Peterson SL, Daugherty MD. Elife 11 e81606 (2022)
  6. Kinesin-1 autoinhibition facilitates the initiation of dynein cargo transport. Qiu R, Zhang J, Xiang X. J Cell Biol 222 e202205136 (2023)
  7. The meiotic LINC complex component KASH5 is an activating adaptor for cytoplasmic dynein. Garner KEL, Salter A, Lau CK, Gurusaran M, Villemant CM, Granger EP, McNee G, Woodman PG, Davies OR, Burke BE, Allan VJ. J Cell Biol 222 e202204042 (2023)
  8. Nde1 promotes Lis1-mediated activation of dynein. Zhao Y, Oten S, Yildiz A. Nat Commun 14 7221 (2023)
  9. Molecular mechanism of dynein-dynactin complex assembly by LIS1. Singh K, Lau CK, Manigrasso G, Gama JB, Gassmann R, Carter AP. Science 383 eadk8544 (2024)


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