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PDBsum entry 1m9s
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Signaling protein
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PDB id
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1m9s
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Gw domains of the listeria monocytogenes invasion protein inlb are sh3-Like and mediate binding to host ligands.
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Authors
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M.Marino,
M.Banerjee,
R.Jonquières,
P.Cossart,
P.Ghosh.
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Ref.
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EMBO J, 2002,
21,
5623-5634.
[DOI no: ]
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PubMed id
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Abstract
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InlB, a surface-localized protein of Listeria monocytogenes, induces
phagocytosis in non-phagocytic mammalian cells by activating Met, a receptor
tyrosine kinase. InlB also binds glycosaminoglycans and the protein gC1q-R, two
additional host ligands implicated in invasion. We present the structure of
InlB, revealing a highly elongated molecule with leucine-rich repeats that bind
Met at one end, and GW domains that dissociably bind the bacterial surface at
the other. Surprisingly, the GW domains are seen to resemble SH3 domains.
Despite this, GW domains are unlikely to act as functional mimics of SH3 domains
since their potential proline-binding sites are blocked or destroyed. However,
we do show that the GW domains, in addition to binding glycosaminoglycans, bind
gC1q-R specifically, and that this binding requires release of InlB from the
bacterial surface. Dissociable attachment to the bacterial surface via the GW
domains may be responsible for restricting Met activation to a small, localized
area of the host cell and for coupling InlB-induced host membrane dynamics with
bacterial proximity during invasion.
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Figure 3.
Figure 3 GW domains resemble SH3 domains. (A) Ribbon
representation of GW and SH3 domains. Left: the Abl SH3 domain
(blue), with bound peptide (green, backbone representation with
prolines shown). The three peptide-binding pockets are numbered.
Middle: InlB GW domain 2. Right: superposition of Abl SH3 (blue)
and InlB GW (red), in C[  ]representation.
(B) Structure-based sequence alignment of InlB GW domain 2, the
L.monocytogenes p60 SH3b domain and the Abl SH3 domain. Residues
responsible for peptide binding in the Abl SH3 domain are marked
with numbers corresponding to binding pockets. Core residues
conserved in GW and Abl are in blue, and secondary structure is
indicated for GW domain 2 (top) and Abl (bottom). Gray shading
marks the RT-loop, a red star indicates the intramolecular
proline contact in InlB site 3, and a blue star indicates the
substituted residue at InlB site 2. (C) Peptide-binding sites of
Abl SH3 (blue, and bound peptide in green) and equivalent
locations in InlB GW domains (red). (D) Molecular surface
representations of the Abl SH3 domain and InlB GW domain 2.
Numbers correspond to proline-binding sites (blue) in Abl and
potential sites in the GW domain (blue). The RT-loop is colored
red, and peptide bound to the SH3 domain is in green.
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Figure 5.
Figure 5 Surface features of InlB GW domains. (A) Top: ribbon
representation of the three InlB GW domains. The first GW domain
is proteolytically sensitive and cleaved from the second and
third protease-resistant GW domains at Leu464. Middle:
electrostatic surface potential of the GW domains (red = -10 kT,
blue = +10 kT). Bottom: exposed hydrophobic residues (green)
mapped to the molecular surface of the GW domains. The black
arrow indicates the hydrophobic groove between domains 1 and 2.
(B) Basis for GW[A]–GW[B] pairwise association. Top: ribbon
representations of GW[A] domains (left) and GW[B] domains
(right). Bottom: molecular surface representation (green,
hydrophobic; red, acidic; blue, basic), with GW[A] and GW[B]
rotated to show interface residues (numbered).
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The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
EMBO J
(2002,
21,
5623-5634)
copyright 2002.
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