TY - JOUR
T1 - DipM controls multiple autolysins and mediates a regulatory feedback loop promoting cell constriction in Caulobacter crescentus
AU - Izquierdo-Martinez, Adrian
AU - Billini, Maria
AU - Miguel-Ruano, Vega
AU - Hernández-Tamayo, Rogelio
AU - Richter, Pia
AU - Biboy, Jacob
AU - Batuecas, María T.
AU - Glatter, Timo
AU - Vollmer, Waldemar
AU - Graumann, Peter L.
AU - Hermoso, Juan A.
AU - Thanbichler, Martin
N1 - Funding Information:
We thank Aleksandra Zielińska for help in the initial phase of the project, Manuel Osorio-Valeriano for advice on protein purification and biochemistry, Julia Rosum and Olga Ebers for excellent technical assistance, Daniela Vollmer for the purification of peptidoglycan, and the staff of the ALBA Synchrotron facility for support during crystallographic data collection. This work was supported by the University of Marburg (core funding to P.L.G. and M.T.), the Max Planck Society (Max Planck Fellowship to M.T.), the German Research Foundation (DFG; project 269423233—TRR 174 to P.L.G.), the United Kingdom Research and Innovation (UKRI) Strategic Priorities Fund (grant EP/T002778/1 to W.V.), the Spanish Agency of Research at the Ministry of Science and Innovation (grant PID2020-115331GB-I00 to J.A.H.) and the Swiss National Science Foundation (grant CRSII5_198737/1 to J.A.H.). A.I.-M. was a fellow of the International Max Planck Research School for Environmental, Cellular and Molecular Microbiology (IMPRS-Mic).
Funding Information:
We thank Aleksandra Zielińska for help in the initial phase of the project, Manuel Osorio-Valeriano for advice on protein purification and biochemistry, Julia Rosum and Olga Ebers for excellent technical assistance, Daniela Vollmer for the purification of peptidoglycan, and the staff of the ALBA Synchrotron facility for support during crystallographic data collection. This work was supported by the University of Marburg (core funding to P.L.G. and M.T.), the Max Planck Society (Max Planck Fellowship to M.T.), the German Research Foundation (DFG; project 269423233—TRR 174 to P.L.G.), the United Kingdom Research and Innovation (UKRI) Strategic Priorities Fund (grant EP/T002778/1 to W.V.), the Spanish Agency of Research at the Ministry of Science and Innovation (grant PID2020-115331GB-I00 to J.A.H.) and the Swiss National Science Foundation (grant CRSII5_198737/1 to J.A.H.). A.I.-M. was a fellow of the International Max Planck Research School for Environmental, Cellular and Molecular Microbiology (IMPRS-Mic).
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - Proteins with a catalytically inactive LytM-type endopeptidase domain are important regulators of cell wall-degrading enzymes in bacteria. Here, we study their representative DipM, a factor promoting cell division in Caulobacter crescentus. We show that the LytM domain of DipM interacts with multiple autolysins, including the soluble lytic transglycosylases SdpA and SdpB, the amidase AmiC and the putative carboxypeptidase CrbA, and stimulates the activities of SdpA and AmiC. Its crystal structure reveals a conserved groove, which is predicted to represent the docking site for autolysins by modeling studies. Mutations in this groove indeed abolish the function of DipM in vivo and its interaction with AmiC and SdpA in vitro. Notably, DipM and its targets SdpA and SdpB stimulate each other’s recruitment to midcell, establishing a self-reinforcing cycle that gradually increases autolytic activity as cytokinesis progresses. DipM thus coordinates different peptidoglycan-remodeling pathways to ensure proper cell constriction and daughter cell separation.
AB - Proteins with a catalytically inactive LytM-type endopeptidase domain are important regulators of cell wall-degrading enzymes in bacteria. Here, we study their representative DipM, a factor promoting cell division in Caulobacter crescentus. We show that the LytM domain of DipM interacts with multiple autolysins, including the soluble lytic transglycosylases SdpA and SdpB, the amidase AmiC and the putative carboxypeptidase CrbA, and stimulates the activities of SdpA and AmiC. Its crystal structure reveals a conserved groove, which is predicted to represent the docking site for autolysins by modeling studies. Mutations in this groove indeed abolish the function of DipM in vivo and its interaction with AmiC and SdpA in vitro. Notably, DipM and its targets SdpA and SdpB stimulate each other’s recruitment to midcell, establishing a self-reinforcing cycle that gradually increases autolytic activity as cytokinesis progresses. DipM thus coordinates different peptidoglycan-remodeling pathways to ensure proper cell constriction and daughter cell separation.
UR - http://www.scopus.com/inward/record.url?scp=85164404422&partnerID=8YFLogxK
U2 - 10.1038/s41467-023-39783-w
DO - 10.1038/s41467-023-39783-w
M3 - Article
C2 - 37433794
AN - SCOPUS:85164404422
SN - 2041-1723
VL - 14
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 4095
ER -