A novel fibronectin type III module binding motif identified on C-terminus of Leptospira immunoglobulin-like protein, LigB.
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.
Lin
Yi-Pin
YP
Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Greenwood
Alex
A
Yan
Weiwei
W
Nicholson
Linda K
LK
Sharma
Yogendra
Y
McDonough
Sean P
SP
Chang
Yung-Fu
YF
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
D000942:Antigens, Bacterial; D005353:Fibronectins; C487006:LigB-m protein, Leptospira interrogans
Nat Rev Drug Discov. 2006 Sep;5(9):730-9
16888652
Nature. 2003 May 8;423(6936):177-81
12736686
J Biol Chem. 2003 Jul 4;278(27):24600-7
12716896
Mol Microbiol. 2004 May;52(3):631-41
15101971
J Mol Biol. 1988 May 5;201(1):201-17
3418697
J Biomol NMR. 1995 Nov;6(3):277-93
8520220
J Magn Reson. 2011 Dec;213(2):276-94
22152348
J Med Microbiol. 2004 Oct;53(Pt 10):975-984
15358819
Infect Immun. 2006 Mar;74(3):1745-50
16495547
J Vet Sci. 2008 Jun;9(2):133-44
18487934
Infect Immun. 2008 Dec;76(12):5826-33
18809657
FEMS Microbiol Lett. 2000 Apr 1;185(1):17-22
10731601
J Biol Chem. 2008 Sep 12;283(37):25140-25149
18625711
Biochemistry. 1992 Feb 18;31(6):1647-51
1737021
J Biol Chem. 1995 Nov 3;270(44):26025-8
7592795
Emerg Infect Dis. 2004 Mar;10(3):406-12
15109405
J Biol Chem. 2004 Apr 16;279(16):15850-9
14749329
Biochem Biophys Res Commun. 2007 Oct 19;362(2):443-8
17707344
J Med Chem. 2001 Aug 2;44(16):2565-74
11472210
Infect Immun. 2002 Nov;70(11):5924-30
12379666
Mol Microbiol. 2004 Apr;52(2):345-55
15066025