title: Structure of internalin, a major invasion protein of Listeria monocytogenes, in complex with its human receptor E-cadherin.
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.
authors.affiliation: Department of Structural Biology, German Research Center for Biotechnology (GBF), Mascheroder Weg 1, D-38124, Braunschweig, Germany.
authors.forename: Wolf Dieter
authors.initials: WD
authors.lastname: Schubert
authors.forename: Claus
authors.initials: C
authors.lastname: Urbanke
authors.forename: Thilo
authors.initials: T
authors.lastname: Ziehm
authors.forename: Viola
authors.initials: V
authors.lastname: Beier
authors.forename: Matthias P
authors.initials: MP
authors.lastname: Machner
authors.forename: Eugen
authors.initials: E
authors.lastname: Domann
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wehland
authors.forename: Trinad
authors.initials: T
authors.lastname: Chakraborty
authors.forename: Dirk W
authors.initials: DW
authors.lastname: Heinz
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry*; D015820:Cadherins / Q000737:chemistry*; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007477:Ions; D007930:Leucine / Q000737:chemistry; D008089:Listeria monocytogenes / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D014461:Ultracentrifugation; D014961:X-Ray Diffraction
chemical_list: D001426:Bacterial Proteins; D015820:Cadherins; D007477:Ions; C069761:internalin protein, Bacteria; D007930:Leucine