ZapG (YhcB/DUF1043), a novel cell division protein in gamma-proteobacteria linking the Z-ring to septal peptidoglycan synthesis

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Mehla, J., G. Liechti, R. Morgenstein, M. Brockett, N. Sakhawalkar, J.H. Caufield, J.H. Hunt, S. Vorobiev, X. Rong, and P. Uetz (2021) ZapG (YhcB/DUF1043), a novel cell division protein in gamma-proteobacteria linking the Z-ring to septal peptidoglycan synthesis Journal of Biological Chemistry in press: https://doi.org/10.1016/j.jbc.2021.100700.

Abstract

YhcB, a poorly understood protein conserved across gamma-proteobacteria, contains a Domain of Unknown Function (DUF 1043) and an N-terminal transmembrane domain. Here we used an integrated approach including X-ray crystallography, genetics and molecular biology to investigate the function and structure of YhcB.

The E. coli yhcB knock-out strain does not grow at 45°C and is hypersensitive to cell-wall acting antibiotics, even in stationary phase. The deletion of yhcB leads to filamentation, abnormal FtsZ ring formation, and aberrant septa development. The Z-ring is essential for the positioning of the septa and the initiation of cell division. We found that YhcB interacts with proteins of the divisome (e.g., FtsI, FtsQ) and elongasome (e.g., RodZ, RodA). Seven of these interactions are also conserved in Yersinia pestis and/or Vibrio cholerae. Furthermore, we mapped the amino acid residues likely involved in the interactions of YhcB with FtsI and RodZ. The 2.8 Å crystal structure of the cytosolic domain of Haemophilus ducreyi YhcB shows a unique tetrameric α-helical coiled-coil structure likely to be involved in linking the Z ring to the septal peptidoglycan synthesizing complexes. In summary, YhcB is a conserved and conditionally essential protein that plays a role in cell division, and consequently affects envelope biogenesis. Based on these findings, we propose to rename YhcB to ZapG (Z-ring associated protein G). This study will serve as a starting point for future studies on this protein family and on how cells transit from exponential to stationary survival.

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