The structures of natively assembled clathrin-coated vesicles

Area of Science:

• Cell Biology
• Structural Biology
• Molecular Mechanisms of Trafficking

Background:

• Clathrin-coated vesicles (CCVs) are crucial for intracellular and intercellular transport of proteins and nutrients.
• While individual clathrin-coated vesicle components are well-characterized, their assembled structures with membranes and cargo remain largely unknown.
• Understanding CCV assembly is key to deciphering cellular trafficking pathways.

Purpose of the Study:

• To determine the structures of natively assembled clathrin-coated vesicles in various configurations.
• To elucidate the role of adaptor protein complexes in the organization and geometry of CCVs.
• To propose a structural model for CCV assembly driven by adaptor-cargo interactions.

Main Methods:

• Cryo-electron tomography was used to visualize natively assembled clathrin-coated vesicles.
• Analysis focused on the arrangement of clathrin heavy chain (CHC) and adaptor protein complexes.
• Computational modeling was employed to propose a structural model of CCV assembly.

Main Results:

• The study revealed how adaptor β2 appendages crosslink adjacent clathrin heavy chain (CHC) β-propellers within CCVs.
• Adaptor protein densities were observed to be enriched in the hexagonal faces of CCVs.
• A detailed structural model illustrates adaptor protein 2 forming an assembly hub that directs the formation of pentagonal and hexagonal faces.

Conclusions:

• Natively assembled clathrin-coated vesicles exhibit specific structural arrangements dictated by adaptor proteins.
• Adaptor proteins act as a central hub, orchestrating the assembly of CCV lattice structures.
• This provides a mechanistic understanding of how CCV geometry is controlled during cargo selection and vesicle formation.