PDBsum entry 5a31

Cell cycle

PDB id: 5a31

Contents

Protein chains

1441 a.a.

84 a.a.

524 a.a.

55 a.a.

56 a.a.

498 a.a.

25 a.a.

730 a.a.

504 a.a.

182 a.a.

59 a.a.

703 a.a.

685 a.a.

491 a.a.

162 a.a.

386 a.a.

21 a.a.

24 a.a.

13 a.a.

484 a.a.

Metals

_ZN ×3

PDB id:

5a31

Name:

Cell cycle

Title:

Structure of the human apc-cdh1-hsl1-ubch10 complex.

Structure:

Anaphase-promoting complex subunit 1. Chain: a. Synonym: apc1, cyclosome subunit 1, mitotic checkpoint regulator, testis-specific gene 24 protein. Engineered: yes. Anaphase-promoting complex subunit 11. Chain: b. Synonym: apc11, cyclosome subunit 11, hepatocellular carcinoma-assoc iated ring finger protein.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Expression_system_taxid: 7111

Authors:

L.Chang,Z.Zhang,J.Yang,S.H.Mclaughlin,D.Barford

Key ref:

L.Chang et al. (2015). Atomic structure of the APC/C and its mechanism of protein ubiquitination. Nature, 522, 450-454. PubMed id: 26083744 DOI: 10.1038/nature14471

Date:

26-May-15 Release date: 18-Nov-15

Protein chain

Q9H1A4  (APC1_HUMAN) -  Anaphase-promoting complex subunit 1 from Homo sapiens

Seq: 1944 a.a.

Struc: 1441 a.a.*

Protein chain

Q9NYG5  (APC11_HUMAN) -  Anaphase-promoting complex subunit 11 from Homo sapiens

Seq: 84 a.a.

Struc: 84 a.a.*

Protein chain

Q9UJX2  (CDC23_HUMAN) -  Cell division cycle protein 23 homolog from Homo sapiens

Seq: 597 a.a.

Struc: 524 a.a.*

Protein chain

P60006  (APC15_HUMAN) -  Anaphase-promoting complex subunit 15 from Homo sapiens

Seq: 121 a.a.

Struc: 55 a.a.*

Protein chain

Q96DE5  (APC16_HUMAN) -  Anaphase-promoting complex subunit 16 from Homo sapiens

Seq: 110 a.a.

Struc: 56 a.a.

Protein chains

P30260  (CDC27_HUMAN) -  Cell division cycle protein 27 homolog from Homo sapiens

Seq: 824 a.a.

Struc: 498 a.a.*

Protein chains

Q8NHZ8  (CDC26_HUMAN) -  Anaphase-promoting complex subunit CDC26 from Homo sapiens

Seq: 85 a.a.

Struc: 25 a.a.

Protein chain

Q9UJX5  (APC4_HUMAN) -  Anaphase-promoting complex subunit 4 from Homo sapiens

Seq: 808 a.a.

Struc: 730 a.a.*

Protein chains

Q13042  (CDC16_HUMAN) -  Cell division cycle protein 16 homolog from Homo sapiens

Seq: 620 a.a.

Struc: 504 a.a.*

Protein chain

Q9UM13  (APC10_HUMAN) -  Anaphase-promoting complex subunit 10 from Homo sapiens

Seq: 185 a.a.

Struc: 182 a.a.

Protein chain

Q9BS18  (APC13_HUMAN) -  Anaphase-promoting complex subunit 13 from Homo sapiens

Seq: 74 a.a.

Struc: 59 a.a.

Protein chain

Q9UJX6  (ANC2_HUMAN) -  Anaphase-promoting complex subunit 2 from Homo sapiens

Seq: 822 a.a.

Struc: 703 a.a.*

Protein chain

Q9UJX4  (APC5_HUMAN) -  Anaphase-promoting complex subunit 5 from Homo sapiens

Seq: 755 a.a.

Struc: 685 a.a.*

Protein chain

Q9UJX2  (CDC23_HUMAN) -  Cell division cycle protein 23 homolog from Homo sapiens

Seq: 597 a.a.

Struc: 491 a.a.*

Protein chain

O00762  (UBE2C_HUMAN) -  Ubiquitin-conjugating enzyme E2 C from Homo sapiens

Seq: 179 a.a.

Struc: 162 a.a.*

Protein chain

P53197  (CDH1_YEAST) -  APC/C activator protein CDH1 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 566 a.a.

Struc: 386 a.a.*

Protein chain

No UniProt id for this chain

Struc: 21 a.a.

Protein chain

No UniProt id for this chain

Struc: 24 a.a.

Protein chain

No UniProt id for this chain

Struc: 13 a.a.

Protein chains

Q9UJX3  (APC7_HUMAN) -  Anaphase-promoting complex subunit 7 from Homo sapiens

Seq: 565 a.a.

Struc: 484 a.a.*

* PDB and UniProt seqs differ at 295 residue positions (black crosses)

Enzyme reactions

• Enzyme class 2: Chain Q: E.C.2.3.2.23 - E2 ubiquitin-conjugating enzyme.
• Reaction: S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [E2 ubiquitin-conjugating enzyme]-L-cysteine = [E1 ubiquitin-activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L- cysteine
• Enzyme class 3: Chain Q: E.C.2.3.2.24 - (E3-independent) E2 ubiquitin-conjugating enzyme.
• Reaction: S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E1 ubiquitin-activating enzyme]-L-cysteine + N₆- monoubiquitinyl-[acceptor protein]-L-lysine

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

DOI no: 10.1038/nature14471

Nature 522:450-454 (2015)

PubMed id: 26083744

Atomic structure of the APC/C and its mechanism of protein ubiquitination.

L.Chang, Z.Zhang, J.Yang, S.H.McLaughlin, D.Barford.

ABSTRACT

The anaphase-promoting complex (APC/C) is a multimeric RING E3 ubiquitin ligase that controls chromosome segregation and mitotic exit. Its regulation by coactivator subunits, phosphorylation, the mitotic checkpoint complex and interphase early mitotic inhibitor 1 (Emi1) ensures the correct order and timing of distinct cell-cycle transitions. Here we use cryo-electron microscopy to determine atomic structures of APC/C-coactivator complexes with either Emi1 or a UbcH10-ubiquitin conjugate. These structures define the architecture of all APC/C subunits, the position of the catalytic module and explain how Emi1 mediates inhibition of the two E2s UbcH10 and Ube2S. Definition of Cdh1 interactions with the APC/C indicates how they are antagonized by Cdh1 phosphorylation. The structure of the APC/C with UbcH10-ubiquitin reveals insights into the initiating ubiquitination reaction. Our results provide a quantitative framework for the design of future experiments to investigate APC/C functions in vivo.