Lateral interactions between protofilaments of the bacterial tubulin homolog FtsZ are essential for cell division.

Fenghui Guan,Yang Liu,Xin-Hua Feng,Jiayu Yu,Jie Yu,Kerwyn Casey Huang,Zengyi Chang,Sheng Ye,Ying Li

doi:10.7554/elife.35578

Fenghui Guan, Yang Liu + Show 7 more

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https://doi.org/10.7554/elife.35578

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Abstract

The prokaryotic tubulin homolog FtsZ polymerizes into protofilaments, which further assemble into higher-order structures at future division sites to form the Z-ring, a dynamic structure essential for bacterial cell division. The precise nature of interactions between FtsZ protofilaments that organize the Z-ring and their physiological significance remain enigmatic. In this study, we solved two crystallographic structures of a pair of FtsZ protofilaments, and demonstrated that they assemble in an antiparallel manner through the formation of two different inter-protofilament lateral interfaces. Our in vivo photocrosslinking studies confirmed that such lateral interactions occur in living cells, and disruption of the lateral interactions rendered cells unable to divide. The inherently weak lateral interactions enable FtsZ protofilaments to self-organize into a dynamic Z-ring. These results have fundamental implications for our understanding of bacterial cell division and for developing antibiotics that target this key process.

Highlights

Bacterial cytokinesis is initiated by the formation of a ring-like structure termed the Z-ring, a polymeric assembly of the essential tubulin homolog FtsZ at future division sites (Bi and Lutkenhaus, 1991)
Our electron microscopy analysis showed that Mycobacterium tuberculosis FtsZ (MtbFtsZ) and FtsZ from Escherichia coli (EcFtsZ) are able to form protofilament bundles in vitro in the presence of DEAE-dextran (Figure 1A,B)
Guided by the similarities in amino acid sequence and tertiary structure between MtbFtsZ and Staphylococcus aureus FtsZ (SaFtsZ), as well as the two lateral interfaces we have identified in MtbFtsZ filaments, we attempted to construct a model for sheet-like structures of FtsZ filaments

Summary

Introduction

Bacterial cytokinesis is initiated by the formation of a ring-like structure termed the Z-ring, a polymeric assembly of the essential tubulin homolog FtsZ at future division sites (Bi and Lutkenhaus, 1991). Once formed, the Z-ring serves as a scaffold to recruit other cell division proteins that collectively constitute the divisome (Dajkovic and Lutkenhaus, 2006). The Z-ring constricts at the leading edge of the invaginating septum, eventually causing a mother cell to divide into two daughter cells (Bi and Lutkenhaus, 1991). FtsZ subunits readily assemble into protofilaments in vitro (Mukherjee and Lutkenhaus, 1994; Romberg et al, 2001), and crystal structures of FtsZ protofilaments have been determined for both straight (Matsui et al, 2012; Tan et al, 2012) and curved conformations (Li et al, 2013). FtsZ protofilaments have been observed to further associate via lateral interfaces to form higher-order structures such as sheets

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