The anaphase-promoting complex (APC) is a cell cycle-regulated ubiquitin-pr
otein ligase, composed of at least 11 subunits, that controls progression t
hrough mitosis and G1. Using cryo-electron microscopy and angular reconstit
ution, we have obtained a three-dimensional model of the human APC at a res
olution of 24 Angstrom. The APC has a complex asymmetric structure 140 Angs
trom x 140 Angstrom x 135 Angstrom in size, in which an outer protein wall
surrounds a large inner cavity. We discuss the possibility that this cavity
represents a reaction chamber in which ubiquitination reactions take place
, analogous to the inner cavities formed by other protein machines such as
the 26S proteasome and chaperone complexes. This cage hypothesis could help
to explain the great subunit complexity of the APC.