文献类型：期刊文献

英文题名：Leptospira Immunoglobulin-Like Protein B Interacts with the 20th Exon of Human Tropoelastin Contributing to Leptospiral Adhesion to Human Lung Cells

作者：Hsieh, Ching-Lin[1];Tseng, Andrew[1];He, Hongxuan[2];Kuo, Chih-Jung[3];Wang, Xuannian[1,4];Chang, Yung-Fu[1]

第一作者：Hsieh, Ching-Lin

通讯作者：Chang, YF[1]

机构：[1]Cornell Univ, Coll Vet Med, Dept Populat Med & Diagnost Sci, Ithaca, NY 14853 USA;[2]Chinese Acad Sci, Inst Zool, Natl Res Ctr Wildlife Borne Dis, Beijing, Peoples R China;[3]Natl Chung Hsing Univ, Dept Vet Med, Taichung, Taiwan;[4]Xinxiang Univ, Res Ctr Biotechnol, Xinxiang, Peoples R China

第一机构：Cornell Univ, Coll Vet Med, Dept Populat Med & Diagnost Sci, Ithaca, NY 14853 USA

通讯机构：[1]corresponding author), Cornell Univ, Coll Vet Med, Dept Populat Med & Diagnost Sci, Ithaca, NY 14853 USA.

年份：2017

卷号：7

期号：MAY

外文期刊名：FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY

收录：;Scopus(收录号：2-s2.0-85027495488);WOS:【SCI-EXPANDED(收录号:WOS:000437343900001)】；

基金：This work was supported in part by the Technology Foundation (CAT) Biotechnology Research (CAT) and Development Corporation (BRDC).

语种：英文

外文关键词：LigB; Leptospira; tropoelastin; outer surface protein; extracellular matrix proteins; protein-protein interaction

摘要：Leptospira immunoglobulin-like protein B (LigB), a surface adhesin, is capable of mediating the attachment of pathogenic leptospira to the host through interaction with various components of the extracellular matrix (ECM). Human tropoelastin (HTE), the building block of elastin, confers resilience and elasticity to lung, and other tissues. Previously identified Ig-like domains of LigB, including LigB4 and LigB12, bind to HTE, which is likely to promote Leptospira adhesion to lung tissue. However, the molecular mechanism that mediates the LigB-HTE interaction is unclear. In this study, the LigB-binding site on HTE was further pinpointed to a N-terminal region of the 20th exon of HTE (HTE20N). Alanine mutants of basic and aromatic residues on HTE20N significantly reduced binding to the LigB. Additionally, HTE-binding site was narrowed down to the first beta-sheet of LigB12. On this binding surface, residues F1054, D1061, A1065, and D1066 were critical for the association with HTE. Most importantly, the recombinant HTE truncates could diminish the binding of LigB to human lung fibroblasts (WI-38) by 68%, and could block the association of LigA-expressing L. biflexa to lung cells by 61%. These findings should expand our understanding of leptospiral pathogenesis, particularly in pulmonary manifestations of leptospirosis.