the terminal immunoglobulin-like repeats of liga and ligb of leptospira enhance their binding to gelatin binding domain of fibronectin and host cells联赛的终端immunoglobulin-like重复和ligb钩端螺旋体增强约束力的明胶绑定域纤连蛋白和宿主细胞.pdfVIP

The Terminal Immunoglobulin-Like Repeats of LigA and LigB of Leptospira Enhance Their Binding to Gelatin Binding Domain of Fibronectin and Host Cells 1 2 3 1 Yi-Pin Lin , Sean P. McDonough , Yogendra Sharma , Yung-Fu Chang * 1 Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America, 2 Department of Biomedical Science, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America, 3 Center for Cellular and Molecular Biology, Hyderabad, India Abstract Leptospira spp. are pathogenic spirochetes that cause the zoonotic disease leptospirosis. Leptospiral immunoglobulin (Ig)- like protein B (LigB) contributes to the binding of Leptospira to extracellular matrix proteins such as fibronectin, fibrinogen, laminin, elastin, tropoelastin and collagen. A high-affinity Fn-binding region of LigB has been localized to LigBCen2, which contains the partial 11th and full 12th Ig-like repeats (LigBCen2R) and 47 amino acids of the non-repeat region (LigBCen2NR) of LigB. In this study, the gelatin binding domain of fibronectin was shown to interact with LigBCen2R (KD = 1.9160.40 mM). Not only LigBCen2R but also other Ig-like domains of Lig proteins including LigAVar7’-8, LigAVar10, LigAVar11, LigAVar12, LigAVar13, LigBCen7’-8, and LigBCen9 bind to GBD. Interestingly, a large gain in affinity was achieved through an avidity effect, with the terminal domains, 13th (LigA) or 12th (LigB) Ig-like repeat of Lig protein (LigAVar7’-13 and LigBCen7’-12) enhancing binding affinity approximately 51 and 28 fold, respectively, compared to recombinant proteins without this terminal repeat. In addition, the inhibited effect on M