Structural organization of the anaphase-promoting complex bound to the mitotic activator Slp1.

The anaphase-promoting complex/cyclosome (APC/C) is a conserved multisubunit E3 ubiquitin (Ub) ligase required to signal the degradation of key cell-cycle regulators. Using single particle cryo-electron microscopy (cryo-EM), we have determined a three-dimensional (3D) structure of the core APC/C from Schizosaccharomyces pombe bound to the APC/C activator Slp1/Cdc20. At the 27 A resolution of our density map, the APC/C is a triangular-shaped structure, approximately 19x17x15 nm in size, with a deep internal cavity and a prominent horn-like protrusion emanating from a lip of the cavity. Using antibody labeling and mutant analysis, we have localized 12 of 13 core APC/C components, as well as the position of the activator Slp1, enabling us to propose a structural model of APC/C organization. Comparison of the APC/C with another multiprotein E3 ligase, the SCF complex, uncovers remarkable structural similarities.

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