Chemical Basis of Peptidoglycan Discrimination by PrkC, a Key Kinase Involved in Bacterial Resuscitation from Dormancy

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• 作者：Flavia Squeglia ; Roberta Marchetti ; Alessia Ruggiero ; Rosa Lanzetta ; Daniela Marasco ; Jonathan Dworkin ; Maxim Petoukhov ; Antonio Molinaro ; Rita Berisio ; Alba Silipo
• 刊名：Journal of the American Chemical Society
• 出版年：2011
• 出版时间：December 28, 2011
• 年：2011
• 卷：133
• 期：51
• 页码：20676-20679
• 全文大小：274K
• 年卷期：v.133,no.51(December 28, 2011)
• ISSN：1520-5126

文摘

Bacterial Ser/Thr kinases modulate a wide number of cellular processes. In Bacillus subtilis, the Ser/Thr kinase PrkC has been shown to induce germination of bacterial spores in response to DAP-type but not Lys-type cell wall muropeptides. Muropeptides are a clear molecular signal that growing conditions are promising, since they are produced during cell wall peptidoglycan remodeling associated with cell growth and division of neighboring bacteria. However, whether muropeptides are able to bind the protein physically and how the extracellular region is able to distinguish the two types of muropeptides remains unclear. Here we tackled the important question of how the extracellular region of PrkC (EC-PrkC) senses muropeptides. By coupling NMR techniques and protein mutagenesis, we exploited the structural requirements necessary for recognition and binding and proved that muropeptides physically bind to EC-PrkC through DAP-moiety-mediated interactions with an arginine residue, Arg500, belonging to the protein C-terminal PASTA domain. Notably, mutation of this arginine completely suppresses muropeptide binding. Our data provide the first molecular clues into the mechanism of sensing of muropeptides by PrkC.