PDBsum entry 5khu

Cell cycle

PDB id: 5khu

Contents

Protein chains

1374 a.a.*

16 a.a.*

463 a.a.*

56 a.a.*

473 a.a.*

25 a.a.*

706 a.a.*

504 a.a.*

169 a.a.*

43 a.a.*

627 a.a.*

608 a.a.*

219 a.a.*

378 a.a.*

333 a.a.*

183 a.a.*

9 a.a.*

396 a.a.*

432 a.a.*

* C-alpha coords only

PDB id:

5khu

Name:

Cell cycle

Title:

Model of human anaphase-promoting complex/cyclosome (apc15 deletion mutant), in complex with the mitotic checkpoint complex (apc/c-cdc20- mcc) based on cryo em data at 4.8 angstrom resolution

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- associated ring finger protein.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: anapc1, tsg24. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Gene: anapc11, hspc214. Gene: cdc23, anapc8. Gene: anapc16, c10orf104, cenp-27.

Authors:

M.Yamaguchi,R.Vanderlinden,P.Dube,H.Stark,B.Schulman

Key ref:

M.Yamaguchi et al. (2016). Cryo-EM of Mitotic Checkpoint Complex-Bound APC/C Reveals Reciprocal and Conformational Regulation of Ubiquitin Ligation. Mol Cell, 63, 593-607. PubMed id: 27522463 DOI: 10.1016/j.molcel.2016.07.003

Date:

15-Jun-16 Release date: 07-Sep-16

Protein chain

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

Seq: 1944 a.a.

Struc: 1374 a.a.*

Protein chain

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

Seq: 84 a.a.

Struc: 16 a.a.

Protein chains

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

Seq: 597 a.a.

Struc: 463 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: 473 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: 706 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: 169 a.a.

Protein chain

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

Seq: 74 a.a.

Struc: 43 a.a.

Protein chain

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

Seq: 822 a.a.

Struc: 627 a.a.*

Protein chain

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

Seq: 755 a.a.

Struc: 608 a.a.*

Protein chain

O60566  (BUB1B_HUMAN) -  Mitotic checkpoint serine/threonine-protein kinase BUB1 beta from Homo sapiens

Seq: 1050 a.a.

Struc: 219 a.a.

Protein chain

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

Seq: 499 a.a.

Struc: 378 a.a.

Protein chain

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

Seq: 499 a.a.

Struc: 333 a.a.*

Protein chain

Q13257  (MD2L1_HUMAN) -  Mitotic spindle assembly checkpoint protein MAD2A from Homo sapiens

Seq: 205 a.a.

Struc: 183 a.a.

Protein chain

No UniProt id for this chain

Struc: 9 a.a.

Protein chain

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

Seq: 565 a.a.

Struc: 396 a.a.

Protein chain

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

Seq: 565 a.a.

Struc: 432 a.a.

* PDB and UniProt seqs differ at 9 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chain Q: E.C.2.7.11.1 - non-specific serine/threonine protein kinase.
• Reaction:
  1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
  2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/j.molcel.2016.07.003

Mol Cell 63:593-607 (2016)

PubMed id: 27522463

Cryo-EM of Mitotic Checkpoint Complex-Bound APC/C Reveals Reciprocal and Conformational Regulation of Ubiquitin Ligation.

M.Yamaguchi, R.VanderLinden, F.Weissmann, R.Qiao, P.Dube, N.G.Brown, D.Haselbach, W.Zhang, S.S.Sidhu, J.M.Peters, H.Stark, B.A.Schulman.

ABSTRACT

The mitotic checkpoint complex (MCC) coordinates proper chromosome biorientation on the spindle with ubiquitination activities of CDC20-activated anaphase-promoting complex/cyclosome (APC/C(CDC20)). APC/C(CDC20) and two E2s, UBE2C and UBE2S, catalyze ubiquitination through distinct architectures for linking ubiquitin (UB) to substrates and elongating polyUB chains, respectively. MCC, which contains a second molecule of CDC20, blocks APC/C(CDC20)-UBE2C-dependent ubiquitination of Securin and Cyclins, while differentially determining or inhibiting CDC20 ubiquitination to regulate spindle surveillance, checkpoint activation, and checkpoint termination. Here electron microscopy reveals conformational variation of APC/C(CDC20)-MCC underlying this multifaceted regulation. MCC binds APC/C-bound CDC20 to inhibit substrate access. However, rotation about the CDC20-MCC assembly and conformational variability of APC/C modulate UBE2C-catalyzed ubiquitination of MCC's CDC20 molecule. Access of UBE2C is limiting for subsequent polyubiquitination by UBE2S. We propose that conformational dynamics of APC/C(CDC20)-MCC modulate E2 activation and determine distinctive ubiquitination activities as part of a response mechanism ensuring accurate sister chromatid segregation.