PDBsum entry 1m9s

Signaling protein

PDB id: 1m9s

Contents

Protein chain

523 a.a. *

Ligands

SO4

Metals

_TB ×7

Waters ×65

* Residue conservation analysis

PDB id:

1m9s

Name:

Signaling protein

Title:

Crystal structure of internalin b (inlb), a listeria monocytogenes virulence protein containing sh3-like domains.

Structure:

Internalin b. Chain: a. Engineered: yes

Source:

Listeria monocytogenes. Organism_taxid: 1639. Gene: inlb. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

2.65Å R-factor: 0.273 R-free: 0.302

Authors:

M.Marino,M.Banerjee,R.Jonquieres,P.Cossart,P.Ghosh

Key ref:

M.Marino et al. (2002). GW domains of the Listeria monocytogenes invasion protein InlB are SH3-like and mediate binding to host ligands. EMBO J, 21, 5623-5634. PubMed id: 12411480 DOI: 10.1093/emboj/cdf558

Date:

29-Jul-02 Release date: 06-Nov-02

Protein chain

P0DQD2  (INLB_LISMO) -  Internalin B from Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e)

Seq: 630 a.a.

Struc: 523 a.a.*

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

DOI no: 10.1093/emboj/cdf558

EMBO J 21:5623-5634 (2002)

PubMed id: 12411480

GW domains of the Listeria monocytogenes invasion protein InlB are SH3-like and mediate binding to host ligands.

M.Marino, M.Banerjee, R.Jonquières, P.Cossart, P.Ghosh.

ABSTRACT

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.

Selected figure(s)

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.

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).

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2002, 21, 5623-5634) copyright 2002.

Figures were selected by the author.