PDBsum entry 5a0f

Signaling protein

PDB id: 5a0f

Contents

Protein chain

178 a.a.

Ligands

GDP

SO4

NDG

Waters ×80

PDB id:

5a0f

Name:

Signaling protein

Title:

Crystal structure of yersinia afp18-modified rhoa

Structure:

Transforming protein rhoa. Chain: a. Fragment: residues 1-181. Synonym: ras-like gtp-binding protein rho, rho cdna clone 12, h12. Engineered: yes. Other_details: glycosylation at y 34

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

2.00Å R-factor: 0.206 R-free: 0.213

Authors:

T.Jank,M.Schimpl,D.M.Van Aalten

Key ref:

T.Jank et al. (2015). Tyrosine glycosylation of Rho by Yersinia toxin impairs blastomere cell behaviour in zebrafish embryos. Nat Commun, 6, 7807. PubMed id: 26190758 DOI: 10.1038/ncomms8807

Date:

20-Apr-15 Release date: 22-Jul-15

Protein chain

P61586  (RHOA_HUMAN) -  Transforming protein RhoA from Homo sapiens

Seq: 193 a.a.

Struc: 178 a.a.

Enzyme reactions

• Enzyme class: E.C.3.6.5.2 - small monomeric GTPase.
• Reaction: GTP + H2O = GDP + phosphate + H⁺

GTP + H2O = GDP (Bound ligand (Het Group name = GDP) corresponds exactly) + phosphate + H(+)

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

reference

DOI no: 10.1038/ncomms8807

Nat Commun 6:7807 (2015)

PubMed id: 26190758

Tyrosine glycosylation of Rho by Yersinia toxin impairs blastomere cell behaviour in zebrafish embryos.

T.Jank, S.Eckerle, M.Steinemann, C.Trillhaase, M.Schimpl, S.Wiese, D.M.van Aalten, W.Driever, K.Aktories.

ABSTRACT

Yersinia species cause zoonotic infections, including enterocolitis and plague. Here we studied Yersinia ruckeri antifeeding prophage 18 (Afp18), the toxin component of the phage tail-derived protein translocation system Afp, which causes enteric redmouth disease in salmonid fish species. Here we show that microinjection of the glycosyltransferase domain Afp18(G) into zebrafish embryos blocks cytokinesis, actin-dependent motility and cell blebbing, eventually abrogating gastrulation. In zebrafish ZF4 cells, Afp18(G) depolymerizes actin stress fibres by mono-O-GlcNAcylation of RhoA at tyrosine-34; thereby Afp18(G) inhibits RhoA activation by guanine nucleotide exchange factors, and blocks RhoA, but not Rac and Cdc42 downstream signalling. The crystal structure of tyrosine-GlcNAcylated RhoA reveals an open conformation of the effector loop distinct from recently described structures of GDP- or GTP-bound RhoA. Unravelling of the molecular mechanism of the toxin component Afp18 as glycosyltransferase opens new perspectives in studies of phage tail-derived protein translocation systems, which are preserved from archaea to human pathogenic prokaryotes.