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PDBsum entry 2odl
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Cell adhesion
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PDB id
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2odl
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References listed in PDB file
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Key reference
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Title
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The structure of the haemophilus influenzae hmw1 pro-Piece reveals a structural domain essential for bacterial two-Partner secretion.
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Authors
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H.J.Yeo,
T.Yokoyama,
K.Walkiewicz,
Y.Kim,
S.Grass,
J.W.Geme.
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Ref.
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J Biol Chem, 2007,
282,
31076-31084.
[DOI no: ]
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PubMed id
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Abstract
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In pathogenic Gram-negative bacteria, many virulence factors are secreted via
the two-partner secretion pathway, which consists of an exoprotein called TpsA
and a cognate outer membrane translocator called TpsB. The HMW1 and HMW2
adhesins are major virulence factors in nontypeable Haemophilus influenzae and
are prototype two-partner secretion pathway exoproteins. A key step in the
delivery of HMW1 and HMW2 to the bacterial surface involves targeting to the
HMW1B and HMW2B outer membrane translocators by an N-terminal region called the
secretion domain. Here we present the crystal structure at 1.92 A of the HMW1
pro-piece (HMW1-PP), a region that contains the HMW1 secretion domain and is
cleaved and released during HMW1 secretion. Structural analysis of HMW1-PP
revealed a right-handed beta-helix fold containing 12 complete parallel coils
and one large extra-helical domain. Comparison of HMW1-PP and the Bordetella
pertussis FHA secretion domain (Fha30) reveals limited amino acid homology but
shared structural features, suggesting that diverse TpsA proteins have a common
structural domain required for targeting to cognate TpsB proteins. Further
comparison of HMW1-PP and Fha30 structures may provide insights into the keen
specificity of TpsA-TpsB interactions.
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Figure 1.
FIGURE 1. Domain organization of HMW1 and model for TPS.
The HMW1 signal sequence (residues 1-68) is shown in yellow, the
HMW1 pro-piece (residues 69-441) is shown in magenta, and the
mature HMW1 adhesin (442-1536) is shown in blue (a large cell
surface structure) and in orange (a small C-terminal anchor).
For clarity, only the secretion process across the outer
membrane is presented. After Sec-dependent export of the HMW1
preproprotein across the inner membrane, the HMW1 secretion
domain interacts with HMW1B, likely in the periplasm,
facilitating translocation of HMW1 across the outer membrane.
Sometime during this translocation process, HMW1-PP is cleaved
and released to the extracellular space (S. Grass and J. W. St.
Geme III, unpublished data). Ultimately, the binding domain of
mature HMW1 is exposed on the tip of the adhesin, away from the
bacterial cell surface, in a position that favors access to host
cells.
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Figure 3.
FIGURE 3. Electrostatic potential surface of HMW1-PP using
GRASP (39). Positive and negative potentials are indicated in
blue and red, respectively. The major pocket formed on the PB2
face is indicated.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2007,
282,
31076-31084)
copyright 2007.
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