Atomic Structure of Clathrin A β Propeller Terminal Domain Joins an α Zigzag Linker

1987a). Sequence analysis of the heavy chain and com-Boston, Massachusetts 02115-5701 parisons with sequences of other proteins have not re-† Howard Hughes Medical Institute and vealed internal repeats, nor have they shown recogniz-‡ Children's Hospital able motifs or domains (Kirchhausen et al., 1987a). Laboratory of Molecular Medicine Rapid assembly and disassembly of coats are central Boston, Massachusetts 02115 to the functions of clathrin in vesicular transport. En-gulfment of receptors and budding of a vesicle require coat assembly; delivery of cargo and fusion with a target Summary membrane require uncoating. In the absence of other proteins and membranes, clathrin trimers can self-Clathrin triskelions form the lattice that organizes reassemble into hollow structures (" cages ") whose lat-cruitment of proteins to coated pits and helps drive tices resemble those of a normal coat (Keen et al., 1979). vesiculation of the lipid bilayer. We report the crystal The proximal and distal legs participate in the interac-structure at 2.6 A ˚ resolution of a 55 kDa N-terminal tions that hold the lattice together (Crowther and Pearse, fragment from the 190 kDa clathrin heavy chain. structure comprises the globular " terminal domain " globular terminal domain projects inward toward the and the linker that joins it to the end of a triskelion membrane (Kirchhausen and Harrison, 1984; Heuser and leg. The terminal domain is a seven-blade ␤ propeller, a structure well adapted to interaction with multiple Proteolysis of assembled cages leads to release of an partners, such as the AP-1 and AP-2 sorting adaptor amino-terminal fragment of about 52–59 kDa, but not complexes and the nonvisual arrestins. The linker is an to disassembly of the lattice (Schmid et al., 1982; Un-␣-helical zigzag emanating from the propeller domain. gewickell et al., 1982). The released fragment includes We propose that this simple motif may extend into the the terminal domain and part of the linker connecting it rest of the clathrin leg. to the distal leg (Kirchhausen and Harrison, 1984). Other proteins in addition to clathrin are required for Introduction assembly under physiological conditions (Keen et al., 1979) and for recruiting cargo to a coated pit (Pearse, Clathrin-coated vesicles transport lipids and proteins 1988). The heterotetrameric clathrin adaptor complexes between intracellular membrane compartments. stimulate coat assembly. pathway, between the plasma membrane and early en-AP-1 and AP-2 interact with the clathrin terminal do-dosomes, and in the secretory pathway, between the main (Contreras and Kirchhausen, unpublished results) trans-Golgi network …