Review
Vesicle coats: structure, function, and general principles of assembly

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The transport of proteins and lipids between distinct cellular compartments is conducted by coated vesicles. These vesicles are formed by the self-assembly of coat proteins on a membrane, leading to collection of the vesicle cargo and membrane bending to form a bud. Scission at the bud neck releases the vesicle. X-ray crystallography and electron microscopy (EM) have recently generated models of isolated coat components and assembled coats. Here, we review these data to present a structural overview of the three main coats: clathrin, COPII, and COPI. The three coats have similar function, common ancestry, and structural similarities, but exhibit fundamental differences in structure and assembly. We describe the implications of structural similarities and differences for understanding the function, assembly principles, and evolution of vesicle coats.

Section snippets

Transport vesicle formation

Eukaryotic cells segregate functions in membrane-delimited compartments. These intracellular compartments are not static: they exchange proteins and lipids continuously in a directional and regulated manner [1]. The exchange of material (cargoes) between compartments is mostly conducted by coated transport vesicles that bud from one membrane and fuse with another. Transport vesicles are hence essential for maintaining organelle identity and lipid homeostasis and for the secretion of proteins.

Structures of coat components

Vast efforts have been invested in unraveling the structures of protein components of the three archetypal coats. X-ray crystallography (Box 1) has provided atomic models of coat fragments and also identified protein–protein interactions involved in coat polymerization 14, 15, 16 and cargo binding 3, 17. In some cases, X-ray crystallography has been combined with single-particle EM (Box 1) to derive the overall shape of coat subcomplexes 18, 19.

Structural homology between coats and evolutionary relationship

The three coat systems perform similar tasks on different membranes, but how are they evolutionarily related? It is widely accepted that the tetrameric adaptors of clathrin share distant sequence homology and structural similarity with the adaptor subcomplex of COPI (β-, γ-, δ-, and ζ-COPs) 38, 47. Sequence similarities between γ- and β-COPs and between ζ- and δ-COPs suggest that the adaptor subcomplex may originate from the duplication of a protodimer of a large and a small subunit [37].

Clathrin cages

The first high-resolution glimpse of how coat proteins assemble into a coated vesicle came from cryo-EM reconstruction of a clathrin cage assembled in vitro from purified cage components (Figure 2 and Box 1). The structure of a hexagonal clathrin barrel with D6 symmetry could accommodate the atomic structures of clathrin, leading to a model for the assembly of clathrin triskelia [18]. Each triskelion represents the vertex of a cage, with the legs of the triskelia intertwining to link the

Concluding remarks

Different assembly principles are found in the three types of coated vesicle. In clathrin and COPII cages, the same building blocks interact by making the same local contacts with the same interaction valence. Changes in size of the cage are accommodated by local flexibility of the triskelion leg (clathrin) or by the interaction angle of different rods (COPII). Clathrin cages purified from brain and COPII cages assembled with the adaptor Sec23 can deviate from point-group symmetry to form

Acknowledgments

The writing of this review was supported by a grant from the Deutsche Forschungsgemeinschaft within SFB638 (A16) to J.A.G.B. and F.T.W.

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