کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5913737 | 1162700 | 2016 | 9 صفحه PDF | دانلود رایگان |
Cholesterol-dependent cytolysins (CDCs) contribute to various pathogenesis by Gram-positive bacterial pathogens. Among them, pneumolysin (PLY) produced by Streptococcus pneumoniae is a major contributor to pneumococcal infections. Despite numerous studies of the cytolytic mechanism of PLY, little structural information on its interactions with a specific receptor of the cell membrane is available. We report here the first crystal structures of PLY in an apo-form and in a ternary complex with two mannoses at 2.8Â Ã and 2.5Â Ã resolutions, respectively. Both structures contained one monomer in an asymmetric unit and were comprised of four discontinuous domains, similar to CDC structures reported previously. The ternary complex structure showed that loop 3 and the undecapeptide region in domain 4 might contribute to cellular recognition by binding to mannose, as a component of a specific cell-surface receptor. Moreover, mutational studies and docking simulations for four residues (Leu431, Trp433, Thr459, and Leu460) in domain 4 indicated that Leu431 and Trp433 in the undecapeptide might be involved in the binding of cholesterol, together with the Thr459-Leu460 pair in loop 1. Our results provide structure-based molecular insights into the interaction of PLY with the target cell membrane, including the binding of mannose and cholesterol.
Journal: Journal of Structural Biology - Volume 193, Issue 2, February 2016, Pages 132-140