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PMID: 18082611 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

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

Molecular cell ·Vol. 28 ·No. 5 ·2007-12-14 ·Pages 871-85

Ohi MD, Feoktistova A, Ren L, Yip C, Cheng Y, Chen JS, Yoon HJ, Wall JS, Huang Z, Penczek PA, Gould KL, Walz T

Abstract

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.

MeSH Terms
Anaphase-Promoting Complex-Cyclosome Cdc20 Proteins Cell Cycle Proteins/chemistry,metabolism Chromatography, Affinity Cryoelectron Microscopy Immunoblotting Mitosis/physiology Models, Molecular Mutagenesis, Site-Directed Mutation Protein Conformation Schizosaccharomyces/genetics,growth & development,metabolism Schizosaccharomyces pombe Proteins/chemistry,metabolism Ubiquitin-Protein Ligase Complexes/chemistry,isolation & purification,metabolism Ubiquitin-Protein Ligases/chemistry,isolation & purification,metabolism Ubiquitination
Chemicals
Cdc20 Proteins Cell Cycle Proteins Schizosaccharomyces pombe Proteins slp1 protein, S pombe Ubiquitin-Protein Ligase Complexes Anaphase-Promoting Complex-Cyclosome Ubiquitin-Protein Ligases
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Ohi Melanie D
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Feoktistova Anna
Ren Liping
Yip Calvin
Cheng Yifan
Chen Jun-Song
Yoon Hyun-Joo
Wall Joseph S
Huang Zhong
Penczek Pawel A
Gould Kathleen L
Walz Thomas
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Article Info
Journal
Molecular cell
Abbr.
Mol Cell
ISSN
1097-2765
DOI
10.1016/j.molcel.2007.10.003
Published
2007-12-14
Pages
871-85
Language
English
Region
United States
NLM ID
9802571
PMCID
PMC2197158
Subset
IM
Grants
NIGMS NIH HHS · GM 60635 · United States
NIGMS NIH HHS · P01 GM062580 · United States
NIBIB NIH HHS · P41 EB002181 · United States
NIGMS NIH HHS · R01 GM060635 · United States
NIGMS NIH HHS · GM62580 · United States
NIGMS NIH HHS · P01 GM062580-06A16830 · United States
NIGMS NIH HHS · P01 GM064692 · United States
NIBIB NIH HHS · 5 P41 EB2181 · United States
External Links
PubMed source DOI: 10.1016/j.molcel.2007.10.003 PMC Full Text View journal details
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