Structure of Shigella IpgB2 in complex with human RhoA: implications for the mechanism of bacterial guanine nucleotide exchange factor mimicry.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
AuthorsKlink, Björn U
Heidler, Thomas V
Stradal, Theresia E B
Heinz, Dirk W
MetadataShow full item record
AbstractA 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.
CitationStructure of Shigella IpgB2 in complex with human RhoA: implications for the mechanism of bacterial guanine nucleotide exchange factor mimicry. 2010, 285 (22):17197-208 J. Biol. Chem.
AffiliationDivision of Structural Biology, Helmholtz Zentrum für Infektionsforschung, D-38124 Braunschweig, Germany.
The following license files are associated with this item:
- The role of Mg2+ cofactor in the guanine nucleotide exchange and GTP hydrolysis reactions of Rho family GTP-binding proteins.
- Authors: Zhang B, Zhang Y, Wang Z, Zheng Y
- Issue date: 2000 Aug 18
- Real-time NMR study of guanine nucleotide exchange and activation of RhoA by PDZ-RhoGEF.
- Authors: Gasmi-Seabrook GM, Marshall CB, Cheung M, Kim B, Wang F, Jang YJ, Mak TW, Stambolic V, Ikura M
- Issue date: 2010 Feb 19
- Structural determinants of RhoA binding and nucleotide exchange in leukemia-associated Rho guanine-nucleotide exchange factor.
- Authors: Kristelly R, Gao G, Tesmer JJ
- Issue date: 2004 Nov 5
- The guanine nucleotide exchange factor Tiam1: a Janus-faced molecule in cellular signaling.
- Authors: Boissier P, Huynh-Do U
- Issue date: 2014 Mar
- Bacterial guanine nucleotide exchange factors SopE-like and WxxxE effectors.
- Authors: Bulgin R, Raymond B, Garnett JA, Frankel G, Crepin VF, Berger CN, Arbeloa A
- Issue date: 2010 Apr