PDBsum entry 3lxr

Signaling protein/rhoa-binding protein

PDB id: 3lxr

Contents

Protein chains

180 a.a. *

181 a.a. *

Ligands

GDP

SO4 ×3

Waters ×484

* Residue conservation analysis

PDB id:

3lxr

Name:

Signaling protein/rhoa-binding protein

Title:

Shigella ipgb2 in complex with human rhoa and gdp (complex c)

Structure:

Transforming protein rhoa. Chain: a. Fragment: residues 2-181. Synonym: h12. Engineered: yes. Ipgb2. Chain: f. Synonym: ipgb2, probably secreted by the mxi-spa secretion machinery. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: rhoa. Expressed in: escherichia coli. Expression_system_taxid: 562. Shigella flexneri. Organism_taxid: 623. Gene: ipgb2.

Resolution:

1.68Å R-factor: 0.172 R-free: 0.219

Authors:

B.U.Klink,S.Barden,T.V.Heidler,C.Borchers,M.Ladwein,T.E.B.Stradal, K.Rottner,D.W.Heinz

Key ref:

B.U.Klink et al. (2010). Structure of Shigella IpgB2 in complex with human RhoA: implications for the mechanism of bacterial guanine nucleotide exchange factor mimicry. J Biol Chem, 285, 17197-17208. PubMed id: 20363740

Date:

25-Feb-10 Release date: 31-Mar-10

Protein chain

P61586  (RHOA_HUMAN) -  Transforming protein RhoA from Homo sapiens

Seq: 193 a.a.

Struc: 180 a.a.

Protein chain

Q9AJW7  (Q9AJW7_SHIFL) -  IpgB2 from Shigella flexneri

Seq: 188 a.a.

Struc: 181 a.a.

Enzyme reactions

• Enzyme class 2: Chain A: 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(+)

• Enzyme class 3: Chain F: E.C.?

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.

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

reference

J Biol Chem 285:17197-17208 (2010)

PubMed id: 20363740

Structure of Shigella IpgB2 in complex with human RhoA: implications for the mechanism of bacterial guanine nucleotide exchange factor mimicry.

B.U.Klink, S.Barden, T.V.Heidler, C.Borchers, M.Ladwein, T.E.Stradal, K.Rottner, D.W.Heinz.

ABSTRACT

A common theme in bacterial pathogenesis is the manipulation of eukaryotic cells by targeting the cytoskeleton. This is in most cases achieved either by modifying actin, or indirectly via activation of key regulators controlling actin dynamics such as Rho-GTPases. A novel group of bacterial virulence factors termed the WXXXE family has emerged as guanine nucleotide exchange factors (GEFs) for these GTPases. The precise mechanism of nucleotide exchange, however, has remained unclear. Here we report the structure of the WXXXE-protein IpgB2 from Shigella flexneri and its complex with human RhoA. We unambiguously identify IpgB2 as a bacterial RhoA-GEF and dissect the molecular mechanism of GDP release, an essential prerequisite for GTP binding. Our observations uncover that IpgB2 induces conformational changes on RhoA mimicking DbI- but not DOCK family GEFs. We also show that dissociation of the GDP.Mg(2+) complex is preceded by the displacement of the metal ion to the alpha-phosphate of the nucleotide, diminishing its affinity to the GTPase. These data refine our understanding of the mode of action not only of WXXXE GEFs but also of mammalian GEFs of the DH/PH family.