Molecular basis of the final step of cell division in Streptococcus pneumoniae
Siseth Martínez-Caballero,
Céline Freton,
Rafael Molina,
Sergio G. Bartual,
Virginie Gueguen-Chaignon,
Chryslène Mercy,
Federico Gago,
Kiran V. Mahasenan,
Inés G. Muñoz,
Mijoon Lee,
Dusan Hesek,
Shahriar Mobashery,
Juan A. Hermoso,
Christophe Grangeasse
Affiliations
Siseth Martínez-Caballero
Department of Crystallography and Structural Biology, Instituto de Química-Física “Rocasolano,” Consejo Superior de Investigaciones Científicas, Madrid, Spain
Céline Freton
Molecular Microbiology and Structural Biochemistry, UMR 5086, Université de Lyon, CNRS, Lyon, France
Rafael Molina
Department of Crystallography and Structural Biology, Instituto de Química-Física “Rocasolano,” Consejo Superior de Investigaciones Científicas, Madrid, Spain
Sergio G. Bartual
Department of Crystallography and Structural Biology, Instituto de Química-Física “Rocasolano,” Consejo Superior de Investigaciones Científicas, Madrid, Spain
Virginie Gueguen-Chaignon
SFR Biosciences, Université de Lyon, CNRS UAR3444, ENS de Lyon, INSERM US8, Lyon, France
Chryslène Mercy
Molecular Microbiology and Structural Biochemistry, UMR 5086, Université de Lyon, CNRS, Lyon, France
Federico Gago
Department of Biomedical Sciences & Instituto de Química Médica-CSIC Associated Unit, School of Medicine and Health Sciences, University of Alcalá, 28805 Alcalá de Henares, Spain
Kiran V. Mahasenan
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA
Inés G. Muñoz
Structural Biology Program, Spanish National Cancer Research Center (CNIO), 28029 Madrid, Spain
Mijoon Lee
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA
Dusan Hesek
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA
Shahriar Mobashery
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA
Juan A. Hermoso
Department of Crystallography and Structural Biology, Instituto de Química-Física “Rocasolano,” Consejo Superior de Investigaciones Científicas, Madrid, Spain; Corresponding author
Christophe Grangeasse
Molecular Microbiology and Structural Biochemistry, UMR 5086, Université de Lyon, CNRS, Lyon, France; Corresponding author
Summary: Bacterial cell-wall hydrolases must be tightly regulated during bacterial cell division to prevent aberrant cell lysis and to allow final separation of viable daughter cells. In a multidisciplinary work, we disclose the molecular dialogue between the cell-wall hydrolase LytB, wall teichoic acids, and the eukaryotic-like protein kinase StkP in Streptococcus pneumoniae. After characterizing the peptidoglycan recognition mode by the catalytic domain of LytB, we further demonstrate that LytB possesses a modular organization allowing the specific binding to wall teichoic acids and to the protein kinase StkP. Structural and cellular studies notably reveal that the temporal and spatial localization of LytB is governed by the interaction between specific modules of LytB and the final PASTA domain of StkP. Our data collectively provide a comprehensive understanding of how LytB performs final separation of daughter cells and highlights the regulatory role of eukaryotic-like kinases on lytic machineries in the last step of cell division in streptococci.
