Cryo-electron tomography reveals that dynactin recruits a team of dyneins for processive motility

Nat Struct Mol Biol. 2018 Mar;25(3):203-207. doi: 10.1038/s41594-018-0027-7. Epub 2018 Feb 7.

Abstract

Cytoplasmic dynein is a protein complex that transports molecular cargo along microtubules (MTs), playing a key role in the intracellular trafficking network. Vertebrate dynein's movement becomes strikingly enhanced upon interacting with dynactin and a cargo adaptor such as BicaudalD2. However, the mechanisms responsible for increased transport activity are not well understood, largely owing to limited structural information. We used cryo-electron tomography (cryo-ET) to visualize the 3D structure of the MT-bound dynein-dynactin complex from Mus musculus and show that the dynactin-cargo adaptor complex binds two dimeric dyneins. This configuration imposes spatial and conformational constraints on both dynein dimers, positioning the four motor domains in proximity to one another and oriented toward the MT minus end. We propose that grouping multiple dyneins onto a single dynactin scaffold promotes collective force production, increased processivity, and unidirectional movement, suggesting mechanistic parallels to axonemal dynein. These findings provide structural insights into a previously unknown mechanism for dynein regulation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Dynactin Complex / chemistry*
  • Dynactin Complex / metabolism
  • Dyneins / chemistry*
  • Dyneins / metabolism
  • Electron Microscope Tomography
  • Mice
  • Microtubule-Associated Proteins / chemistry
  • Microtubule-Associated Proteins / metabolism
  • Microtubules / chemistry
  • Microtubules / metabolism
  • Models, Molecular
  • Protein Domains

Substances

  • Bicd2 protein, mouse
  • Dynactin Complex
  • Microtubule-Associated Proteins
  • hook3 protein, mouse
  • Dyneins