PDBsum entry 4ztd

Replication

PDB id

4ztd

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Contents

			Protein chains

					253 a.a.


					12 a.a.

			Ligands

					ALA-GLY-ALA-GLY- ALA

			Waters ×188

PDB id:

4ztd

Links

Name:

Replication

Title:

Crystal structure of human pcna in complex with a traip peptide

Structure:

Proliferating cell nuclear antigen. Chain: a, b, c. Fragment: unp residues 2-254. Synonym: pcna,cyclin. Engineered: yes. Ala-phe-gln-ala-lys-leu-asp-thr-phe-leu-trp-ser. Chain: d, e. Engineered: yes. Ala-gly-ala-gly-ala.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: pcna. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Organism_taxid: 9606

Resolution:

2.20Å

R-factor:

0.205

R-free:

0.234

Authors:

G.Montoya,G.B.Mortuza,F.J.Blanco,A.Ibanez De Opakua

Key ref:

S.Hoffmann et al. (2016). TRAIP is a PCNA-binding ubiquitin ligase that protects genome stability after replication stress. J Cell Biol, 212, 63-75. PubMed id: 26711499 DOI: 10.1083/jcb.201506071

Date:

14-May-15

Release date:

16-Dec-15

PROCHECK

	Headers

	References

Protein chains

P12004 (PCNA_HUMAN) - Proliferating cell nuclear antigen from Homo sapiens

Seq: Struc:					261 a.a. 253 a.a.

Protein chains

Q9BWF2 (TRAIP_HUMAN) - E3 ubiquitin-protein ligase TRAIP from Homo sapiens

Seq: Struc:					469 a.a. 12 a.a.*

Key:

PfamA domain

Secondary structure

CATH domain

* PDB and UniProt seqs differ at 1 residue position (black cross)



		Enzyme reactions

Enzyme class 1:

Chains A, B, C: E.C.?

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Enzyme class 2:

Chains D, E: E.C.2.3.2.27 - RING-type E3 ubiquitin transferase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N₆- ubiquitinyl-[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: 10.1083/jcb.201506071	J Cell Biol 212:63-75 (2016)
PubMed id: 26711499

TRAIP is a PCNA-binding ubiquitin ligase that protects genome stability after replication stress.
S.Hoffmann, S.Smedegaard, K.Nakamura, G.B.Mortuza, M.Räschle, A.Ibañez de Opakua, Y.Oka, Y.Feng, F.J.Blanco, M.Mann, G.Montoya, A.Groth, S.Bekker-Jensen, N.Mailand.

ABSTRACT

Cellular genomes are highly vulnerable to perturbations to chromosomal DNA replication. Proliferating cell nuclear antigen (PCNA), the processivity factor for DNA replication, plays a central role as a platform for recruitment of genome surveillance and DNA repair factors to replication forks, allowing cells to mitigate the threats to genome stability posed by replication stress. We identify the E3 ubiquitin ligase TRAIP as a new factor at active and stressed replication forks that directly interacts with PCNA via a conserved PCNA-interacting peptide (PIP) box motif. We show that TRAIP promotes ATR-dependent checkpoint signaling in human cells by facilitating the generation of RPA-bound single-stranded DNA regions upon replication stress in a manner that critically requires its E3 ligase activity and is potentiated by the PIP box. Consequently, loss of TRAIP function leads to enhanced chromosomal instability and decreased cell survival after replication stress. These findings establish TRAIP as a PCNA-binding ubiquitin ligase with an important role in protecting genome integrity after obstacles to DNA replication.