SepF is the FtsZ anchor in archaea, with features of an ancestral cell division system

Nika Pende,Anna Sartori-Rupp,Martín Graña,Anne Marie Wehenkel,Patrick England,Hayk Palabikyan,Adrià Sogues,Simon K.-M R Rittmann,Simonetta Gribaldo,Pedro M Alzari,Daniela Megrian

doi:10.1038/s41467-021-23099-8

Abstract

Most archaea divide by binary fission using an FtsZ-based system similar to that of bacteria, but they lack many of the divisome components described in model bacterial organisms. Notably, among the multiple factors that tether FtsZ to the membrane during bacterial cell constriction, archaea only possess SepF-like homologs. Here, we combine structural, cellular, and evolutionary analyses to demonstrate that SepF is the FtsZ anchor in the human-associated archaeon Methanobrevibacter smithii. 3D super-resolution microscopy and quantitative analysis of immunolabeled cells show that SepF transiently co-localizes with FtsZ at the septum and possibly primes the future division plane. M. smithii SepF binds to membranes and to FtsZ, inducing filament bundling. High-resolution crystal structures of archaeal SepF alone and in complex with the FtsZ C-terminal domain (FtsZCTD) reveal that SepF forms a dimer with a homodimerization interface driving a binding mode that is different from that previously reported in bacteria. Phylogenetic analyses of SepF and FtsZ from bacteria and archaea indicate that the two proteins may date back to the Last Universal Common Ancestor (LUCA), and we speculate that the archaeal mode of SepF/FtsZ interaction might reflect an ancestral feature. Our results provide insights into the mechanisms of archaeal cell division and pave the way for a better understanding of the processes underlying the divide between the two prokaryotic domains.

Highlights

Most archaea divide by binary fission using an FtsZ-based system similar to that of bacteria, but they lack many of the divisome components described in model bacterial organisms
A similar evolutionary history can be inferred from FtsZ, which shows a clear separation among archaeal and bacterial homologs (Supplementary Fig. 15), and suggests an ancient gene duplication in Archaea giving rise to FtsZ1 and FtsZ2 paralogues, consistent with recent reports[10]. These results strongly suggest that SepF and FtsZ emerged before the divergence of Archaea and Bacteria, likely being part of the division machinery in the Last Universal Common Ancestor (LUCA) and subsequently coevolved in the two prokaryotic domains
In contrast to the well-studied FtsA, the function of SepF has been analyzed in a few bacteria so far[16,17,19,20,21,22,28], and only one crystal structure in complex with FtsZ is currently available from C. glutamicum[21]

Summary

Introduction

Most archaea divide by binary fission using an FtsZ-based system similar to that of bacteria, but they lack many of the divisome components described in model bacterial organisms. High-resolution crystal structures of archaeal SepF alone and in complex with the FtsZ C-terminal domain (FtsZCTD) reveal that SepF forms a dimer with a homodimerization interface driving a binding mode that is different from that previously reported in bacteria. The human “archaeome”—whose research is still in its infancy—is receiving growing attention, as an imbalance of archaeal methanogens has been linked to various pathologies such as Inflammatory Bowel Disease, multiple sclerosis, anorexia and colorectal cancer[4] Despite this potential clinical relevance, knowledge on the process of cytokinesis and the involved actors is still very partial in Archaea with respect to Bacteria. The first crystal structure of a bacterial SepF-FtsZ complex was only recently obtained from the Actinobacterium Corynebacterium glutamicum[21] It showed that SepF forms a functional dimer that is required for FtsZ binding[21]. SepF binds to the FtsZCTD through a conserved pocket and interacts with residues at the α-helical interface of the functional dimer[21]

Methods

Results

Conclusion