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A Structural Model for the Core Nup358-BicD2 Interface.

James M Gibson1, Xiaoxin Zhao2, M Yusuf Ali3

  • 1Department of Biological Sciences, Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, 110 8th Street, Troy, NY 12180, USA.

Biomolecules
|October 28, 2023
PubMed
Summary
This summary is machine-generated.

The dynein adaptor Bicaudal D2 (BicD2) binds to Nup358 via two interfaces, revealing structural mechanisms for cargo selection in neuronal development.

Keywords:
AlphaFold2Bicaudal D2Nup358dyneinintracellular transportnuclear positioning

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Area of Science:

  • Cellular biology
  • Structural biology
  • Neuroscience

Background:

  • Dynein motors drive essential minus-end-directed transport along microtubules.
  • Bicaudal D2 (BicD2) is a key adaptor protein that links cellular cargo to the dynein motor.
  • Nup358 is a cargo recognized by BicD2, crucial for nuclear positioning in differentiating brain progenitor cells.

Purpose of the Study:

  • To elucidate the structural details of the BicD2-Nup358 interaction.
  • To understand how BicD2 selects Nup358 cargo for dynein-mediated transport.
  • To provide a structural basis for BicD2's role in brain development.

Main Methods:

  • Computational modeling using AlphaFold2, HADDOCK, and ClusPro.
  • Site-directed mutagenesis to probe the BicD2-Nup358 interface.
  • Analysis of protein-protein interactions and structural interfaces.

Main Results:

  • The Nup358 cargo-recognition α-helix binds BicD2 (residues 747-774) in an anti-parallel helical bundle, stabilized by salt bridges.
  • A secondary interface involves an intrinsically disordered Nup358 region binding BicD2 (residues 774-800).
  • This BicD2 region also binds Rab6, suggesting competition for cargo adaptors.

Conclusions:

  • Established the structural basis for Nup358 cargo recognition by BicD2.
  • Identified dual binding interfaces, including a novel interaction with an intrinsically disordered region.
  • Highlighted the mechanism of cargo selection by BicD2, impacting neuronal development pathways.