Cryo-EM shows how dynactin recruits two dyneins for faster movement

Nature. 2018 Feb 7;554(7691):202-206. doi: 10.1038/nature25462.

Abstract

Dynein and its cofactor dynactin form a highly processive microtubule motor in the presence of an activating adaptor, such as BICD2. Different adaptors link dynein and dynactin to distinct cargoes. Here we use electron microscopy and single-molecule studies to show that adaptors can recruit a second dynein to dynactin. Whereas BICD2 is biased towards recruiting a single dynein, the adaptors BICDR1 and HOOK3 predominantly recruit two dyneins. We find that the shift towards a double dynein complex increases both the force and speed of the microtubule motor. Our 3.5 Å resolution cryo-electron microscopy reconstruction of a dynein tail-dynactin-BICDR1 complex reveals how dynactin can act as a scaffold to coordinate two dyneins side-by-side. Our work provides a structural basis for understanding how diverse adaptors recruit different numbers of dyneins and regulate the motile properties of the dynein-dynactin transport machine.

Publication types

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

MeSH terms

  • Adaptor Proteins, Vesicular Transport / metabolism
  • Animals
  • Biological Transport
  • Cryoelectron Microscopy*
  • Dynactin Complex / metabolism*
  • Dynactin Complex / ultrastructure*
  • Dyneins / metabolism*
  • Dyneins / ultrastructure*
  • Humans
  • Mice
  • Microtubule-Associated Proteins / metabolism
  • Microtubules / metabolism
  • Models, Molecular
  • Movement*
  • Single Molecule Imaging
  • Swine

Substances

  • Adaptor Proteins, Vesicular Transport
  • Bicd2 protein, mouse
  • Bicdl1 protein, mouse
  • Dynactin Complex
  • Microtubule-Associated Proteins
  • hook3 protein, human
  • Dyneins