title: A novel fibronectin type III module binding motif identified on C-terminus of Leptospira immunoglobulin-like protein, LigB.
abstract: Infection by pathogenic strains of Leptospira hinges on the pathogen's ability to adhere to host cells via extracellular matrix such as fibronectin (Fn). Previously, the immunoglobulin-like domains of Leptospira Lig proteins were recognized as adhesins binding to N-terminal domain (NTD) and gelatin binding domain (GBD) of Fn. In this study, we identified another Fn-binding motif on the C-terminus of the Leptospira adhesin LigB (LigBCtv), residues 1708-1712 containing sequence LIPAD with a beta-strand and nascent helical structure. This motif binds to 15th type III modules (15F(3)) (K(D)=10.70 microM), and association (k(on)=600 M(-1)s(-1)) and dissociation (k(off)=0.0129 s(-1)) rate constants represents a slow binding kinetics in this interaction. Moreover, pretreatment of MDCK cells with LigB(1706-1716) blocked the binding of Leptospira by 39%, demonstrating a significant role of LigB(1706-1716) in cellular adhesion. These data indicate that the LIPAD residues (LigB(1708-1712)) of the Leptospira interrogans LigB protein bind 15F(3) of Fn at a novel binding site, and this interaction contributes to adhesion to host cells.
authors.affiliation: Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Yi-Pin
authors.initials: YP
authors.lastname: Lin
authors.forename: Alex
authors.initials: A
authors.lastname: Greenwood
authors.forename: Weiwei
authors.initials: W
authors.lastname: Yan
authors.forename: Linda K
authors.initials: LK
authors.lastname: Nicholson
authors.forename: Yogendra
authors.initials: Y
authors.lastname: Sharma
authors.forename: Sean P
authors.initials: SP
authors.lastname: McDonough
authors.forename: Yung-Fu
authors.initials: YF
authors.lastname: Chang
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D001422:Bacterial Adhesion; D018929:Cell Culture Techniques; D004285:Dogs; D005353:Fibronectins / Q000378:metabolism*; D007919:Leptospira / Q000378:metabolism / Q000472:pathogenicity*; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary / Q000235:genetics
chemical_list: D000942:Antigens, Bacterial; D005353:Fibronectins; C487006:LigB-m protein, Leptospira interrogans
references.citation: Nat Rev Drug Discov. 2006 Sep;5(9):730-9
references.pmid: 16888652
references.citation: Nature. 2003 May 8;423(6936):177-81
references.pmid: 12736686
references.citation: J Biol Chem. 2003 Jul 4;278(27):24600-7
references.pmid: 12716896
references.citation: Mol Microbiol. 2004 May;52(3):631-41
references.pmid: 15101971
references.citation: J Mol Biol. 1988 May 5;201(1):201-17
references.pmid: 3418697
references.citation: J Biomol NMR. 1995 Nov;6(3):277-93
references.pmid: 8520220
references.citation: J Magn Reson. 2011 Dec;213(2):276-94
references.pmid: 22152348
references.citation: J Med Microbiol. 2004 Oct;53(Pt 10):975-984
references.pmid: 15358819
references.citation: Infect Immun. 2006 Mar;74(3):1745-50
references.pmid: 16495547
references.citation: J Vet Sci. 2008 Jun;9(2):133-44
references.pmid: 18487934
references.citation: Infect Immun. 2008 Dec;76(12):5826-33
references.pmid: 18809657
references.citation: FEMS Microbiol Lett. 2000 Apr 1;185(1):17-22
references.pmid: 10731601
references.citation: J Biol Chem. 2008 Sep 12;283(37):25140-25149
references.pmid: 18625711
references.citation: Biochemistry. 1992 Feb 18;31(6):1647-51
references.pmid: 1737021
references.citation: J Biol Chem. 1995 Nov 3;270(44):26025-8
references.pmid: 7592795
references.citation: Emerg Infect Dis. 2004 Mar;10(3):406-12
references.pmid: 15109405
references.citation: J Biol Chem. 2004 Apr 16;279(16):15850-9
references.pmid: 14749329
references.citation: Biochem Biophys Res Commun. 2007 Oct 19;362(2):443-8
references.pmid: 17707344
references.citation: J Med Chem. 2001 Aug 2;44(16):2565-74
references.pmid: 11472210
references.citation: Infect Immun. 2002 Nov;70(11):5924-30
references.pmid: 12379666
references.citation: Mol Microbiol. 2004 Apr;52(2):345-55
references.pmid: 15066025