Pancholi V, Fischetti V A
Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, New York 10021, USA.
J Biol Chem. 1998 Jun 5;273(23):14503-15. doi: 10.1074/jbc.273.23.14503.
The plasmin(ogen) binding property of group A streptococci is incriminated in tissue invasion processes. We have characterized a novel 45-kDa protein displaying strong plasmin(ogen) binding activity from the streptococcal surface. Based on its biochemical properties, we confirmed the identity of this protein as alpha-enolase, a key glycolytic enzyme. Dose-dependent alpha-enolase activity, immune electron microscopy of whole streptococci using specific antibodies, and the opsonic nature of polyclonal and monoclonal antibodies concluded the presence of this protein on the streptococcal surface. We, henceforth, termed the 45-kDa protein, SEN (streptococcal surface enolase). SEN is found ubiquitously on the surface of most streptococcal groups and serotypes and showed significantly greater plasmin(ogen) binding affinity compared with previously reported streptococcal plasminogen binding proteins. Both the C-terminal lysine residue of SEN and a region N-terminal to it play a critical role in plasminogen binding. Results from competitive plasminogen binding inhibition assays and cross-linking studies with intact streptococci indicate that SEN contributes significantly to the overall streptococcal ability to bind plasmin(ogen). Our findings, showing both the protected protease activity of SEN-bound plasmin and SEN-specific immune responses, provide evidence for an important role of SEN in the disease process and post-streptococcal autoimmune diseases.
A组链球菌的纤溶酶（原）结合特性与组织侵袭过程有关。我们从链球菌表面鉴定出一种具有强纤溶酶（原）结合活性的新型45 kDa蛋白。根据其生化特性，我们确定该蛋白为α-烯醇化酶，一种关键的糖酵解酶。α-烯醇化酶活性的剂量依赖性、使用特异性抗体对完整链球菌进行免疫电子显微镜检查以及多克隆和单克隆抗体的调理性质均证实了该蛋白存在于链球菌表面。此后，我们将这种45 kDa蛋白称为SEN（链球菌表面烯醇化酶）。SEN在大多数链球菌群和血清型的表面普遍存在，并且与先前报道的链球菌纤溶酶原结合蛋白相比，显示出明显更高的纤溶酶（原）结合亲和力。SEN的C末端赖氨酸残基及其N末端区域在纤溶酶原结合中都起着关键作用。竞争性纤溶酶原结合抑制试验和与完整链球菌的交联研究结果表明，SEN对链球菌结合纤溶酶（原）的总体能力有显著贡献。我们的研究结果显示了与SEN结合的纤溶酶的受保护蛋白酶活性以及SEN特异性免疫反应，为SEN在疾病过程和链球菌感染后自身免疫性疾病中的重要作用提供了证据。
