title: Leptospira immunoglobulin-like protein B (LigB) binding to the C-terminal fibrinogen αC domain inhibits fibrin clot formation, platelet adhesion and aggregation.
abstract: Leptospira immunoglobulin-like (Lig) proteins including LigA and LigB are adhesins that bind to fibronectin, collagen, laminin and elastin. In addition, Lig proteins are fibrinogen (Fg)-binding proteins, although the physiological role of the Lig-Fg interaction is unclear. In this study, a previously identified Fg-binding region, LigBCen2 (amino acids 1014-1165 of LigB), has been further localized to LigBCen2R, which consists of the partial 11th and entire 12th Ig-like domain (amino acids 1014-1119). LigBCen2R was found to bind to the C-terminal αC domain of Fg (FgαCC; amino acids 392-644 in Fg α chain; isothermal titration calorimetry, K(D) = 0.375 µM; fluorescence spectrometry, K(D) = 0.364 µM). The quenching and blue shift observed for the maximum wavelength intensities of the tryptophan fluorescence spectra for FgαCCY570W upon LigBCen2RW1073C binding suggested an RGD motif close to the sole tryptophan on FgαCCY570W was buried in LigBCen2R upon saturation with FgαCC. A conformational change in LigBCen2R when bound to the FgαCC RGD motif blocked further binding to integrin α(IIb) β3 on platelets, thus preventing their aggregation. LigBCen2R binding to FgαCC reduced clot formation but did not affect plasminogen and tissue-type plasminogen activator interactions with FgαCC. This study is the first to report that a spirochaetal protein binds to the C-terminal αC domain of Fg, which regulates thrombosis and fibrinolysis, and may help explain the pulmonary haemorrhage and thrombocytopenia seen in clinical cases of leptospirosis.
authors.affiliation: Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, NY, USA.
authors.forename: Yi-Pin
authors.initials: YP
authors.lastname: Lin
authors.forename: Sean P
authors.initials: SP
authors.lastname: McDonough
authors.forename: Yogendra
authors.initials: Y
authors.lastname: Sharma
authors.forename: Yung-Fu
authors.initials: YF
authors.lastname: Chang
mesh_terms: D000942:Antigens, Bacterial / Q000378:metabolism*; D005337:Fibrin / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D007919:Leptospira / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation; D011485:Protein Binding
chemical_list: D000942:Antigens, Bacterial; C487006:LigB-m protein, Leptospira interrogans; D010446:Peptide Fragments; C098000:fibrinogen alphaC; D005337:Fibrin; D005340:Fibrinogen