PDBsum entry 4ggc

Cell cycle

PDB id: 4ggc

Contents

Protein chain

313 a.a.

Ligands

MRD ×4

Waters ×443

PDB id:

4ggc

Name:

Cell cycle

Title:

Structural analysis of human cdc20 supports multi-site degron recognition by apc/c

Structure:

Cell division cycle protein 20 homolog. Chain: a. Synonym: p55cdc. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: cdc20. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.

Resolution:

1.35Å R-factor: 0.133 R-free: 0.146

Authors:

X.Luo,W.Tian,D.R.Tomchick

Key ref:

W.Tian et al. (2012). Structural analysis of human Cdc20 supports multisite degron recognition by APC/C. Proc Natl Acad Sci U S A, 109, 18419-18424. PubMed id: 23091007

Date:

06-Aug-12 Release date: 07-Nov-12

Protein chain

Q12834  (CDC20_HUMAN) -  Cell division cycle protein 20 homolog from Homo sapiens

Seq: 499 a.a.

Struc: 313 a.a.

Proc Natl Acad Sci U S A 109:18419-18424 (2012)

PubMed id: 23091007

Structural analysis of human Cdc20 supports multisite degron recognition by APC/C.

W.Tian, B.Li, R.Warrington, D.R.Tomchick, H.Yu, X.Luo.

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.