title: Structural and functional insight into the carbohydrate receptor binding of F4 fimbriae-producing enterotoxigenic Escherichia coli.
abstract: Enterotoxigenic Escherichia coli (ETEC) strains are important causes of intestinal disease in humans and lead to severe production losses in animal farming. A range of fimbrial adhesins in ETEC strains determines host and tissue tropism. ETEC strains expressing F4 fimbriae are associated with neonatal and post-weaning diarrhea in piglets. Three naturally occurring variants of F4 fimbriae (F4ab, F4ac, and F4ad) exist that differ in the primary sequence of their major adhesive subunit FaeG, and each features a related yet distinct receptor binding profile. Here the x-ray structure of FaeGad bound to lactose provides the first structural insight into the receptor specificity and mode of binding by the poly-adhesive F4 fimbriae. A small D'-D″-α1-α2 subdomain grafted on the immunoglobulin-like core of FaeG hosts the carbohydrate binding site. Two short amino acid stretches Phe(150)-Glu(152) and Val(166)-Glu(170) of FaeGad bind the terminal galactose in the lactosyl unit and provide affinity and specificity to the interaction. A hemagglutination-based assay with E. coli expressing mutant F4ad fimbriae confirmed the elucidated co-complex structure. Interestingly, the crucial D'-α1 loop that borders the FaeGad binding site adopts a different conformation in the two other FaeG variants and hints at a heterogeneous binding pocket among the FaeG serotypes.
authors: From the Structural and Molecular Microbiology, VIB Structural Biology Research Center, 1050 Brussels, the Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, and.
authors: Kristof
authors: K
authors: Moonens
authors: From the Structural and Molecular Microbiology, VIB Structural Biology Research Center, 1050 Brussels, the Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, and.
authors: Imke
authors: I
authors: Van den Broeck
authors: From the Structural and Molecular Microbiology, VIB Structural Biology Research Center, 1050 Brussels, the Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, and.
authors: Maia
authors: M
authors: De Kerpel
authors: the Viral Genetics Laboratory, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
authors: Francine
authors: F
authors: Deboeck
authors: From the Structural and Molecular Microbiology, VIB Structural Biology Research Center, 1050 Brussels, the Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, and.
authors: Hanne
authors: H
authors: Raymaekers
authors: From the Structural and Molecular Microbiology, VIB Structural Biology Research Center, 1050 Brussels, the Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, and.
authors: Han
authors: H
authors: Remaut
authors: From the Structural and Molecular Microbiology, VIB Structural Biology Research Center, 1050 Brussels, the Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, and hdegreve@vub.ac.be.
authors: Henri
authors: H
authors: De Greve
mesh_terms: D018830:Adhesins, Escherichia coli / Q000737:chemistry*; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000737:chemistry* / Q000378:metabolism; D015703:Antigens, CD / Q000737:chemistry; D001665:Binding Sites; D018360:Crystallography, X-Ray; D054307:Enterotoxigenic Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism; D036781:Fimbriae Proteins / Q000737:chemistry* / Q000378:metabolism; D005699:Galactosylceramides / Q000737:chemistry; D007785:Lactose / Q000737:chemistry; D007790:Lactosylceramides / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding
chemical_list: D018830:Adhesins, Escherichia coli; D000942:Antigens, Bacterial; D015703:Antigens, CD; D029968:Escherichia coli Proteins; C494388:FaeG protein, E coli; D005699:Galactosylceramides; C026888:K88 antigen, E coli; D007790:Lactosylceramides; D036781:Fimbriae Proteins; C009744:CDw17 antigen; D007785:Lactose
keywords: Bacterial Adhesion; Co-complex; Escherichia coli (E. coli); Lectin; Mutagenesis; Post-weaning Diarrhea; X-ray Crystallography
references: Cell. 2002 Jun 28;109(7):913-23
references: 12110187
references: Acta Crystallogr D Biol Crystallogr. 1998 Nov 1;54(Pt 6 Pt 1):1119-31
references: 10089488
references: Nat Rev Microbiol. 2004 Feb;2(2):123-40
references: 15040260
references: Microbiol Mol Biol Rev. 2007 Dec;71(4):551-75
references: 18063717
references: Infect Immun. 1982 Sep;37(3):891-4
references: 6752028
references: Infect Immun. 1998 Apr;66(4):1613-21
references: 9529089
references: J Mol Biol. 2009 Dec 18;394(5):957-67
references: 19799915
references: PLoS One. 2011;6(9):e23309
references: 21949679
references: Mol Microbiol. 2005 Jan;55(2):441-55
references: 15659162
references: Mol Microbiol. 2010 Apr;76(2):489-502
references: 20345656
references: Infect Immun. 1986 Apr;52(1):18-25
references: 3007359
references: Proc Natl Acad Sci U S A. 2013 Jan 15;110(3):1065-70
references: 23277582
references: J Mol Biol. 2007 May 4;368(3):791-9
references: 17368480
references: Infect Immun. 1992 Mar;60(3):983-8
references: 1347288
references: Anim Health Res Rev. 2005 Jun;6(1):17-39
references: 16164007
references: Appl Environ Microbiol. 2006 Apr;72(4):3005-10
references: 16598008
references: Microb Pathog. 1992 May;12(5):367-75
references: 1354324
references: PLoS One. 2008;3(4):e2040
references: 18446213
references: Infect Immun. 1979 Mar;23(3):700-5
references: 110679
references: Infect Immun. 1994 Dec;62(12):5404-10
references: 7960120
references: Mol Microbiol. 2006 Sep;61(6):1556-68
references: 16930149
references: Biochim Biophys Acta. 1980 Oct 1;632(2):326-35
references: 6774765
references: Mol Microbiol. 1991 Apr;5(4):875-86
references: 1713284
references: J Biol Chem. 2006 Jun 16;281(24):16656-63
references: 16624825
references: Nature. 2011 Jun 2;474(7349):49-53
references: 21637253
references: Curr Opin Struct Biol. 2007 Oct;17(5):506-12
references: 17719218
references: J Health Popul Nutr. 2004 Dec;22(4):370-82
references: 15663170
references: Philos Trans R Soc Lond B Biol Sci. 2012 Apr 19;367(1592):1112-22
references: 22411982
references: Infect Immun. 1993 Sep;61(9):3673-7
references: 8103039
references: Int J Med Microbiol. 2005 Oct;295(6-7):443-54
references: 16238018
references: Mol Microbiol. 1989 May;3(5):645-52
references: 2668694
references: Bioorg Med Chem. 2003 May 15;11(10):2255-61
references: 12713835
references: Cell. 2010 May 14;141(4):645-55
references: 20478255
references: Mol Microbiol. 2012 Oct;86(1):82-95
references: 22812428
references: Gene. 1985;40(2-3):183-90
references: 3007288
references: J Anim Sci. 1998 Feb;76(2):551-6
references: 9498365
references: Mol Microbiol. 2003 Aug;49(3):705-15
references: 12864853
references: Vet Microbiol. 1998 Jan 16;59(2-3):203-12
references: 9549860
references: Infect Immun. 2007 Mar;75(3):1272-9
references: 17178780
references: Adv Exp Med Biol. 1999;473:147-54
references: 10659352
references: Acta Crystallogr D Biol Crystallogr. 1994 Sep 1;50(Pt 5):760-3
references: 15299374
references: Mol Microbiol. 2002 May;44(4):903-15
references: 12010488
references: Cell. 2008 May 16;133(4):640-52
references: 18485872
references: Infect Immun. 2002 May;70(5):2336-43
references: 11953368
references: J Gen Microbiol. 1975 Feb;86(2):228-40
references: 46271
references: Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
references: 15572765
references: Mol Microbiol. 1995 Jun;16(6):1243-57
references: 8577257
references: FEMS Microbiol Rev. 1996 Oct;19(1):25-52
references: 8916554
references: Cell. 2001 Jun 15;105(6):733-43
references: 11440716
references: Infect Immun. 2009 Feb;77(2):699-706
references: 19015246
references: J Bacteriol. 1992 Oct;174(20):6350-8
references: 1400188
references: Infect Immun. 1996 Feb;64(2):606-10
references: 8550214
references: Mol Microbiol. 1992 Jan;6(2):247-55
references: 1372075
references: Acta Pathol Microbiol Scand. 1964;62:439-47
references: 14227889
references: Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):125-32
references: 20124692
references: Trends Microbiol. 1996 Nov;4(11):444-52
references: 8950814
references: Vet Res. 1999 Mar-Jun;30(2-3):259-84
references: 10367358
references: Adv Exp Med Biol. 1997;412:167-73
references: 9192009
references: Infect Immun. 1999 Jan;67(1):165-72
references: 9864211