4GGC
Structural Analysis of Human Cdc20 Supports Multi-site Degron Recognition by APC/C
Summary for 4GGC
| Entry DOI | 10.2210/pdb4ggc/pdb |
| Related | 4GGA |
| Descriptor | Cell division cycle protein 20 homolog, (4R)-2-METHYLPENTANE-2,4-DIOL (3 entities in total) |
| Functional Keywords | cell cycle, mitosis, securin, ubiquitination, wd40 |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasm, cytoskeleton, microtubule organizing center, centrosome : Q12834 |
| Total number of polymer chains | 1 |
| Total formula weight | 35384.81 |
| Authors | Luo, X.,Tian, W.,Tomchick, D.R. (deposition date: 2012-08-06, release date: 2012-11-07, Last modification date: 2024-02-28) |
| Primary citation | Tian, W.,Li, B.,Warrington, R.,Tomchick, D.R.,Yu, H.,Luo, X. Structural analysis of human Cdc20 supports multisite degron recognition by APC/C. Proc.Natl.Acad.Sci.USA, 109:18419-18424, 2012 Cited by PubMed Abstract: The anaphase-promoting complex/cyclosome (APC/C) promotes anaphase onset and mitotic exit through ubiquitinating securin and cyclin B1. The mitotic APC/C activator, the cell division cycle 20 (Cdc20) protein, directly interacts with APC/C degrons--the destruction (D) and KEN boxes. APC/C(Cdc20) is the target of the spindle checkpoint. Checkpoint inhibition of APC/C(Cdc20) requires the binding of a BubR1 KEN box to Cdc20. How APC/C recognizes substrates is not understood. We report the crystal structures of human Cdc20 alone or bound to a BubR1 KEN box. Cdc20 has a disordered N-terminal region and a C-terminal WD40 β propeller with a preformed KEN-box-binding site at its top face. We identify a second conserved surface at the side of the Cdc20 β propeller as a D-box-binding site. The D box of securin, but not its KEN box, is critical for securin ubiquitination by APC/C(Cdc20). Although both motifs contribute to securin ubiquitination by APC/C(Cdh1), securin mutants lacking either motif are efficiently ubiquitinated. Furthermore, D-box peptides diminish the ubiquitination of KEN-box substrates by APC/C(Cdh1), suggesting possible competition between the two motifs. Our results indicate the lack of strong positive cooperativity between the two degrons of securin. We propose that low-cooperativity, multisite target recognition enables APC/C to robustly ubiquitinate diverse substrates and helps to drive cell cycle oscillations. PubMed: 23091007DOI: 10.1073/pnas.1213438109 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.35 Å) |
Structure validation
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