3LYQ

Crystal structure of IpgB2 from Shigella flexneri

Summary for 3LYQ

• Entry DOI: 10.2210/pdb3lyq/pdb
• Related: 3LW8 3LWN 3LXR
• Descriptor: IpgB2, CITRATE ANION, MU-OXO-DIIRON, ... (4 entities in total)
• Functional Keywords: ipgb2, gef, wxxxe, ttss effector protein, bacterial gef, cytoskeleton dynamics, rhoa-binding protein
• Biological source: Shigella flexneri
• Total number of polymer chains: 2
• Total formula weight: 44694.66

Authors

Klink, B.U.,Barden, S.,Heidler, T.V.,Borchers, C.,Ladwein, M.,Stradal, T.E.B.,Rottner, K.,Heinz, D.W. (deposition date: 2010-02-28, release date: 2010-03-31, Last modification date: 2024-03-20)

Primary citation

Klink, B.U.,Barden, S.,Heidler, T.V.,Borchers, C.,Ladwein, M.,Stradal, T.E.B.,Rottner, K.,Heinz, D.W.
Structure of Shigella IPGB2 in complex with human RhoA: Implications for the mechanism of bacterial GEF-mimicry
J.Biol.Chem., 285:17197-17208, 2010

PubMed 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.

PubMed: 20363740
DOI: 10.1074/jbc.M110.107953

Experimental method

X-RAY DIFFRACTION (2.3 Å)