PDBsum entry 4ow2

Toxin

PDB id: 4ow2

Contents

Protein chains

448 a.a.

Waters ×59

PDB id:

4ow2

Name:

Toxin

Title:

Yopm from yersinia enterocolitica wa-314

Structure:

Yop effector yopm. Chain: a, b, c, d. Fragment: unp residues 34-481. Engineered: yes

Source:

Yersinia enterocolitica subsp. Enterocolitica wa-314. Organism_taxid: 1194086. Gene: ywa314_20912. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

3.20Å R-factor: 0.183 R-free: 0.201

Authors:

A.Rumm,M.Perbandt,M.Aepfelbacher

Key ref:

L.Berneking et al. (2016). Immunosuppressive Yersinia Effector YopM Binds DEAD Box Helicase DDX3 to Control Ribosomal S6 Kinase in the Nucleus of Host Cells. PLoS Pathog, 12, e1005660. PubMed id: 27300509 DOI: 10.1371/journal.ppat.1005660

Date:

30-Jan-14 Release date: 04-Mar-15

Protein chains

A0A0J9X1Z0  (A0A0J9X1Z0_YEREN) -  Yop effector YopM from Yersinia enterocolitica subsp. enterocolitica WA-314

Seq: 448 a.a.

Struc: 448 a.a.

DOI no: 10.1371/journal.ppat.1005660

PLoS Pathog 12:e1005660 (2016)

PubMed id: 27300509

Immunosuppressive Yersinia Effector YopM Binds DEAD Box Helicase DDX3 to Control Ribosomal S6 Kinase in the Nucleus of Host Cells.

L.Berneking, M.Schnapp, A.Rumm, C.Trasak, K.Ruckdeschel, M.Alawi, A.Grundhoff, A.G.Kikhney, F.Koch-Nolte, F.Buck, M.Perbandt, C.Betzel, D.I.Svergun, M.Hentschke, M.Aepfelbacher.

ABSTRACT

Yersinia outer protein M (YopM) is a crucial immunosuppressive effector of the plaque agent Yersinia pestis and other pathogenic Yersinia species. YopM enters the nucleus of host cells but neither the mechanisms governing its nucleocytoplasmic shuttling nor its intranuclear activities are known. Here we identify the DEAD-box helicase 3 (DDX3) as a novel interaction partner of Y. enterocolitica YopM and present the three-dimensional structure of a YopM:DDX3 complex. Knockdown of DDX3 or inhibition of the exportin chromosomal maintenance 1 (CRM1) increased the nuclear level of YopM suggesting that YopM exploits DDX3 to exit the nucleus via the CRM1 export pathway. Increased nuclear YopM levels caused enhanced phosphorylation of Ribosomal S6 Kinase 1 (RSK1) in the nucleus. In Y. enterocolitica infected primary human macrophages YopM increased the level of Interleukin-10 (IL-10) mRNA and this effect required interaction of YopM with RSK and was enhanced by blocking YopM's nuclear export. We propose that the DDX3/CRM1 mediated nucleocytoplasmic shuttling of YopM determines the extent of phosphorylation of RSK in the nucleus to control transcription of immunosuppressive cytokines.