PDBsum entry 1o6s

Bacterial infection

PDB id: 1o6s

Contents

Protein chains

461 a.a. *

105 a.a. *

Metals

_CL ×3

_CA ×2

Waters ×537

* Residue conservation analysis

PDB id:

1o6s

Name:

Bacterial infection

Title:

Internalin (listeria monocytogenes) / e-cadherin (human) recognition complex

Structure:

Internalin a. Chain: a. Fragment: functional domain, residues 36-496. Engineered: yes. E-cadherin. Chain: b. Fragment: n-terminal domain, residues 156-253. Engineered: yes

Source:

Listeria monocytogenes. Organism_taxid: 169963. Strain: egd-e. Variant: serovar 1/2a. Atcc: dsmz 20600. Expressed in: escherichia coli. Expression_system_taxid: 511693. Homo sapiens. Human.

Biol. unit:

Dimer (from PDB file)

Resolution:

1.80Å R-factor: 0.171 R-free: 0.221

Authors:

W.-D.Schubert,C.Urbanke,T.Ziehm,V.Beier,M.P.Machner,E.Domann, J.Wehland,T.Chakraborty,D.W.Heinz

Key ref:

W.D.Schubert et al. (2002). Structure of internalin, a major invasion protein of Listeria monocytogenes, in complex with its human receptor E-cadherin. Cell, 111, 825-836. PubMed id: 12526809 DOI: 10.1016/S0092-8674(02)01136-4

Date:

13-Oct-02 Release date: 13-Dec-02

Protein chain

P0DJM0  (INLA_LISMO) -  Internalin A from Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e)

Seq: 800 a.a.

Struc: 461 a.a.

Protein chain

P12830  (CADH1_HUMAN) -  Cadherin-1 from Homo sapiens

Seq: 882 a.a.

Struc: 105 a.a.*

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

DOI no: 10.1016/S0092-8674(02)01136-4

Cell 111:825-836 (2002)

PubMed id: 12526809

Structure of internalin, a major invasion protein of Listeria monocytogenes, in complex with its human receptor E-cadherin.

W.D.Schubert, C.Urbanke, T.Ziehm, V.Beier, M.P.Machner, E.Domann, J.Wehland, T.Chakraborty, D.W.Heinz.

ABSTRACT

Listeria monocytogenes, a food-borne bacterial pathogen, enters mammalian cells by inducing its own phagocytosis. The listerial protein internalin (InlA) mediates bacterial adhesion and invasion of epithelial cells in the human intestine through specific interaction with its host cell receptor E-cadherin. We present the crystal structures of the functional domain of InlA alone and in a complex with the extracellular, N-terminal domain of human E-cadherin (hEC1). The leucine rich repeat (LRR) domain of InlA surrounds and specifically recognizes hEC1. Individual interactions were probed by mutagenesis and analytical ultracentrifugation. These include Pro16 of hEC1, a major determinant for human susceptibility to L. monocytogenes infection that is essential for intermolecular recognition. Our studies reveal the structural basis for host tro-pism of this bacterium and the molecular deception L. monocytogenes employs to exploit the E-cadherin system.

Selected figure(s)

Figure 3.
Figure 3. The N-Terminal Domain of E-CadherinSuperposition with related murine domains: Green – hEC1 (this paper); light blue – murine E-cadherin (Pertz et al., 1999); blue – murine N-cadherin (Tamura et al., 1998). β strand a′ is more closely associated with strand b in hEC1 and is important for intermolecular contacts between hEC1 and InlA′.

Figure 4.
Figure 4. Detailed View of the Interactions between InlA′ and hEC1(A) All residue side chains involved in direct interactions or as ligands to bridging ions/water are indicated in ball-and-stick representation. Residues mutated in this study are underlined. For InlA′ β strands (1–15 and a of Ig-like domain) and adjacent coils are shown in violet. hEC1 is represented by a continuous coil, β strands are indicated by dark-green shading (labels a–g, connecting loops are indicated by two letters to indicate flanking β strands). Cyan-, yellow- and orange-colored spheres represent water, Ca^2+, and Cl^−, respectively.(B) View of the hydrophobic pocket in InlA′, which accommodates Pro16 of hEC1. In addition, the neighboring residues Phe17 (side chain omitted) and Pro18 are involved in specific interactions with InlA′. Hydrogen bonds are indicated by green dotted lines. In murine, E-cadherin Pro16 is replaced by glutamate (yellow model).(C) The octahedrally coordinated Ca^2+ bridging InlA′and hEC1. The refined 2F[O]-F[C] map contoured at 1σ is shown as a translucent surface.

The above figures are reprinted by permission from Cell Press: Cell (2002, 111, 825-836) copyright 2002.

Figures were selected by an automated process.