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Updated: Feb 7, 2026
Assembly and Characterization of Polyelectrolyte Complex Micelles
Published on: March 2, 2020
Structural characterization of a minimal KLC2/Nup358/BicD2 complex
Abstract:
Cellular transport processes along microtubules are often facilitated by multi-motor complexes, which are connected by adapter proteins and cargoes. The nuclear pore protein Nup358, for example, interacts with the dynein adapter Bicaudal D2 (BicD2), which in turn recruits minus-end directed dynein motors and plus-end directed kinesin-1 motors for a nuclear positioning pathway that is essential for brain development. How motor recruitment is regulated by interactions of BicD2 with Nup358 is not well understood. Here, we characterize the structure of a minimal complex of kinesin-1 light chain 2 (KLC2), Nup358 and BicD2 by cryo-electron microscopy and small angle X-ray scattering. KLC2/Nup358 assumes a rod-like structure that increases in thickness, when BicD2 is bound. The addition of BicD2 also shifts the KLC2/Nup358/BicD2 complex towards a 2:2:2 stoichiometry, promoting dimerization at lower protein concentrations than without BicD2. Similarly, the presence of the Nup358/KLC2 interaction results in a shift towards a 2:2:2 stoichiometry. Based on these results, we hypothesize that KLC2 and BicD2 are recruited to Nup358 in a cooperative manner, and cooperativity may be promoted by modulation of the oligomeric state.
Insights
Cellular transport relies on multi-motor protein complexes. This study reveals how Kinesin-1 light chain 2 (KLC2) and Bicaudal D2 (BicD2) cooperatively bind Nup358, influencing motor recruitment for nuclear positioning.
Area of Science:
- Cellular biology
- Molecular motors
- Protein structure and dynamics
Background:
- Cellular transport along microtubules involves multi-motor protein complexes.
- Nuclear pore protein Nup358 interacts with Bicaudal D2 (BicD2) to recruit dynein and kinesin-1 motors for nuclear positioning.
- Regulation of motor recruitment by BicD2-Nup358 interactions is not fully understood.
Purpose of the Study:
- To characterize the structure of a minimal complex of kinesin-1 light chain 2 (KLC2), Nup358, and BicD2.
- To elucidate the mechanism of motor recruitment regulation by BicD2 and Nup358.
Main Methods:
- Cryo-electron microscopy (cryo-EM) to determine complex structure.
- Small-angle X-ray scattering (SAXS) to analyze complex shape and stoichiometry.
- Biochemical assays to study protein interactions and oligomerization.
Main Results:
- KLC2/Nup358 forms a rod-like structure that thickens upon BicD2 binding.
- BicD2 binding shifts the KLC2/Nup358/BicD2 complex towards a 2:2:2 stoichiometry, promoting dimerization.
- Nup358/KLC2 interaction also favors a 2:2:2 stoichiometry.
Conclusions:
- KLC2 and BicD2 are cooperatively recruited to Nup358.
- Cooperative binding is potentially mediated by modulation of the complex's oligomeric state.
- Understanding this mechanism provides insights into nuclear positioning and brain development pathways.
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