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PDBsum entry 3lxr
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Signaling protein/rhoa-binding protein
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PDB id
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3lxr
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References listed in PDB file
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Key reference
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Title
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Structure of shigella ipgb2 in complex with human rhoa: implications for the mechanism of bacterial guanine nucleotide exchange factor mimicry.
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Authors
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B.U.Klink,
S.Barden,
T.V.Heidler,
C.Borchers,
M.Ladwein,
T.E.Stradal,
K.Rottner,
D.W.Heinz.
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Ref.
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J Biol Chem, 2010,
285,
17197-17208.
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PubMed id
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Abstract
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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.
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