title: Chemical basis of peptidoglycan discrimination by PrkC, a key kinase involved in bacterial resuscitation from dormancy.
abstract: 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.
authors: Institute of Biostructures and Bioimaging, Consiglio Nazionale delle Ricerche (CNR), Via Mezzocannone 16, I-80134 Napoli, Italy.
authors: Flavia
authors: F
authors: Squeglia
authors: Roberta
authors: R
authors: Marchetti
authors: Alessia
authors: A
authors: Ruggiero
authors: Rosa
authors: R
authors: Lanzetta
authors: Daniela
authors: D
authors: Marasco
authors: Jonathan
authors: J
authors: Dworkin
authors: Maxim
authors: M
authors: Petoukhov
authors: Antonio
authors: A
authors: Molinaro
authors: Rita
authors: R
authors: Berisio
authors: Alba
authors: A
authors: Silipo
mesh_terms: D001412:Bacillus subtilis / Q000737:chemistry* / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D009154:Mutation; D019906:Nuclear Magnetic Resonance, Biomolecular; D010457:Peptidoglycan / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D013379:Substrate Specificity
chemical_list: D010457:Peptidoglycan; D017346:Protein Serine-Threonine Kinases