分析志贺氏菌毒力因子OspF的选择性
{"_":"Profiling Selectivity for the Virulence Factor OspF.","i":["Shigella"]}
摘要(中文译文)
磷酸苏氨酸裂解酶是一个小家族的细菌毒力因子，在一些革兰阴性病原体感染过程中被分泌进入宿主细胞。磷酸苏氨酸裂解酶催化不可逆的磷酸β-消除反应，将宿主蛋白上的磷酸苏氨酸（pThr）转化为脱氢丁氨酸（Dhb）。在此，我们探索了OspF的底物谱，OspF是一种在感染过程中分泌的磷酸苏氨酸裂解酶，此前已有报道称其可修饰丝裂原活化蛋白激酶（MAPKs）以沉默宿主免疫反应。在本研究中，我们结合合成磷酸肽实验和自下而上的化学蛋白质组学分析来揭示OspF的底物。这些研究不仅表明OspF在MAPK家族内表现出选择性，还揭示OspF在细胞裂解液中和感染过程中可修饰广泛的细胞靶标。利用亲核膦化学探针，我们鉴定并验证了MAPK家族之外的新OspF靶标，包括Rab1A和酪蛋白激酶2β。总之，这些发现为感染中OspF的底物提供了有价值的见解，并强调需要进一步研究以揭示其在发病机制背景下的完整作用。此外，这些数据凸显了OspF和其他磷酸裂解酶作为用于位点特异性蛋白质编辑的新型化学和合成生物学工具的潜在效用。
Abstract
Phosphothreonine lyases are a small family of bacterial virulence factors that are secreted into host cells during infection by some Gram-negative pathogens. Phosphothreonine lyases catalyze an irreversible phosphate β-elimination that converts phosphothreonine (pThr) to dehydrobutyrine (Dhb) on host proteins. Here, we explore the substrate profile for OspF, a phosphothreonine lyase secreted during infection, which has been previously reported to modify mitogen-activated protein kinases (MAPKs) to silence the host immune response. In this work, we use a combination of assays with synthetic phosphopeptides and bottom-up chemoproteomic profiling to uncover the OspF substrates. These studies not only show that OspF exhibits selectivity within the MAPK family but also reveal that OspF modifies a wide range of cellular targets in cellular lysates and during infection. Using a nucleophilic phosphine chemical probe, we identified and validated new OspF targets beyond the MAPK family, including Rab1A and casein kinase 2β. Together, these findings provide valuable insights about OspF substrates in infection and highlight the need for further studies to reveal its full role in the context of pathogenesis. Moreover, these data underscore the potential utility of OspF and other phospholyases as novel chemical and synthetic biology tools for site-specific protein editing.
如何引用
AMA
Nicholas P McCurtin, Ariana Gazaferi, Noah D Novick, Kyungsub Kim, Cammie F Lesser, Rebecca A Scheck. {"_":"Profiling Selectivity for the Virulence Factor OspF.","i":["Shigella"]}. Biochemistry. 2026; doi:10.1021/acs.biochem.6c00109.
APA
Nicholas P McCurtin, Ariana Gazaferi, Noah D Novick, Kyungsub Kim, Cammie F Lesser, Rebecca A Scheck (2026). {"_":"Profiling Selectivity for the Virulence Factor OspF.","i":["Shigella"]}. Biochemistry. https://doi.org/10.1021/acs.biochem.6c00109
GB/T 7714
Nicholas P McCurtin, Ariana Gazaferi, Noah D Novick, Kyungsub Kim, Cammie F Lesser, Rebecca A Scheck. {"_":"Profiling Selectivity for the Virulence Factor OspF.","i":["Shigella"]}[J]. Biochemistry, 2026 doi:10.1021/acs.biochem.6c00109.
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