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

被引:228
作者
Schubert, WD
Urbanke, C
Ziehm, T
Beier, V
Machner, MP
Domann, E
Wehland, J
Chakraborty, T
Heinz, DW
机构
[1] German Res Ctr Biotechnol, Dept Biol Struct, D-38124 Braunschweig, Germany
[2] German Res Ctr Biotechnol, Dept Cell Biol, D-38124 Braunschweig, Germany
[3] Hannover Med Sch, Inst Biophys Chem, D-30623 Hannover, Germany
[4] Univ Giessen, Inst Med Microbiol, D-35385 Giessen, Germany
关键词
D O I
10.1016/S0092-8674(02)01136-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Listeria monocytogenes, a food-borne bacterial pathogen, enters mammalian cells by inducing its own phagocytosis. The listerial protein internalin (InIA) 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 InIA alone and in a complex with the extracellular, N-terminal domain of human E-cadherin (hEC1). The leucine rich repeat (LRR) domain of InIA 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 tropism of this bacterium and the molecular deception L. monocytogenes employs to exploit the E-cadherin system.
引用
收藏
页码:825 / 836
页数:12
相关论文
共 57 条
[1]   THE CCP4 SUITE - PROGRAMS FOR PROTEIN CRYSTALLOGRAPHY [J].
BAILEY, S .
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1994, 50 :760-763
[2]   Inactivation of the srtA gene in Listeria monocytogenes inhibits anchoring of surface proteins and affects virulence [J].
Bierne, H ;
Mazmanian, SK ;
Trost, M ;
Pucciarelli, MG ;
Liu, G ;
Dehoux, P ;
Jänsch, L ;
Garcia-del Portillo, F ;
Schneewind, O ;
Cossart, P .
MOLECULAR MICROBIOLOGY, 2002, 43 (04) :869-881
[3]   C-cadherin ectodomain structure and implications for cell adhesion mechanisms [J].
Boggon, TJ ;
Murray, J ;
Chappuis-Flament, S ;
Wong, E ;
Gumbiner, BM ;
Shapiro, L .
SCIENCE, 2002, 296 (5571) :1308-1313
[4]   FREE R-VALUE - A NOVEL STATISTICAL QUANTITY FOR ASSESSING THE ACCURACY OF CRYSTAL-STRUCTURES [J].
BRUNGER, AT .
NATURE, 1992, 355 (6359) :472-475
[5]   Crystallography & NMR system:: A new software suite for macromolecular structure determination [J].
Brunger, AT ;
Adams, PD ;
Clore, GM ;
DeLano, WL ;
Gros, P ;
Grosse-Kunstleve, RW ;
Jiang, JS ;
Kuszewski, J ;
Nilges, M ;
Pannu, NS ;
Read, RJ ;
Rice, LM ;
Simonson, T ;
Warren, GL .
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1998, 54 :905-921
[6]   Structural and functional diversity in the leucine rich repeat family of proteins [J].
Buchanan, SGS ;
Gay, NJ .
PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY, 1996, 65 (1-2) :1-44
[7]   Surface proteins and the pathogenic potential of Listeria monocytogenes [J].
Cabanes, D ;
Dehoux, P ;
Dussurget, O ;
Frangeul, L ;
Cossart, P .
TRENDS IN MICROBIOLOGY, 2002, 10 (05) :238-+
[8]   Multiple cadherin extracellular repeats mediate homophilic binding and adhesion [J].
Chappuis-Flament, S ;
Wong, E ;
Hicks, LD ;
Kay, CM ;
Gumbiner, BM .
JOURNAL OF CELL BIOLOGY, 2001, 154 (01) :231-243
[9]   Interactions of Listeria monocytogenes with mammalian cells during entry and actin-based movement:: bacterial factors, cellular ligands and signaling [J].
Cossart, P ;
Lecuit, M .
EMBO JOURNAL, 1998, 17 (14) :3797-3806
[10]  
Daniels JJD, 2000, FEMS MICROBIOL LETT, V190, P323, DOI 10.1016/S0378-1097(00)00356-6