Exploring the dynamic partnership between FtsZ and ZapA protein

Researchers explore the structure and molecular basis of the interaction between bacterial cell division-associated proteins FtsZ and ZapA

2025-07-22

(Press-News.org)

Bacterial cell division, a process wherein a single cell divides to form two identical daughter cells, represents one of the most essential biological processes. Understanding the precise mechanism behind this dynamic process can help in the development of targeted ways to inhibit bacterial proliferation.

The process of cell division involves multiple proteins and their complex interactions. FtsZ protein molecules polymerize to form protofibrils that further associate into a ring-like structure called the Z-ring. Z-ring formation is a crucial step in the cell division process, facilitated by multiple FtsZ-associated proteins. ZapA is one such protein, which is conserved widely among multiple bacterial species and is expressed in significantly high levels. The ZapA protein binds to FtsZ protofilaments, assisting in the formation and maintenance of the Z-ring. However, multiple aspects of bacterial cell division remain unexplored, including the exact structure of the FtsZ-ZapA protein complex and the underlying mechanism of interaction.

While previous studies have characterized these proteins separately, researchers wanted to understand their dynamic interaction. Professor Hiroyoshi Matsumura from the College of Life Sciences, Ritsumeikan University, Japan, had led a previous study published in Nature Communications in 2023, titled ‘Structures of a FtsZ single protofilament and a double-helical tube in complex with a monobody,’ which focused on the structure of FtsZ protofilaments. Building on that work, the researchers sought to understand the dynamic interaction between the FtsZ and ZapA proteins.

Now, in a new study led by Prof. Matsumura, published in Nature Communications on July 1, 2025, the researchers have finally been able to gain insights into the cooperative functioning of these two proteins. Dr. Ryo Uehara from Ritsumeikan University, Dr. Takayuki Uchihashi from Nagoya University and ExcCELLs, Dr. Keiichi Namba, Dr. Junso Fujita, and Dr. Kazuki Kasai, all from the University of Osaka, were also involved in this study. “FtsZ is a potential therapeutic target for bacterial infections. Hence, we wanted to understand how it maintains its dynamic nature while interacting with ZapA protein and the overall structure of the complex,” says Prof. Matsumura while explaining the main inspiration behind their research.

For the study, FtsZ and ZapA proteins from the bacteria Klebsiella pneumoniae were analyzed. The scientists utilized cryo-electron microscopy, a high-resolution microscopy technique, to visualize the three-dimensional structure of FtsZ and ZapA. Next, they used high-speed atomic force microscopy to understand the cooperative interaction between the two proteins.

Their analysis revealed that four units of ZapA protein molecules form the ZapA tetramer, which tethers to FtsZ protofilaments to form an asymmetric ladder-like structure. In this ladder-like arrangement, a single FtsZ filament is precisely held between two parallel FtsZ filaments on one side. On the other side, it is tethered to a double anti-parallel protofilament. “In an anti-parallel protofilament, the filaments run alongside each other, but the subunits are aligned in opposite directions,” explains Prof. Matsumura. Thus, ZapA impacts the alignment of the FtsZ filament, which further influences the formation of the Z-ring structure. Furthermore, ZapA and FtsZ were observed to interact extensively over large surface areas, and this contact caused minor structural alterations in FtsZ conformation.

Notably, the team also revealed the existence of electrostatic repulsion within the anti-parallel double filament. This repulsive force is thought to enhance the mobility of FtsZ filaments, enabling them to maintain their dynamic nature without any interference.

The team also captured the real-time dynamics of ZapA-FtsZ interaction. The interaction was found to be dynamic in nature, with repeated binding and dissociation, which helps to maintain the mobility of the filaments. They described the interaction as cooperative binding. “Once ZapA binds to FtsZ, some structural change is observed. This makes the adjacent FtsZ molecule more accessible for the next ZapA molecule,” said Prof. Matsumura while explaining the cooperative interaction.

This study has revealed the intricate mechanism of bacterial cell division, paving the way for the development of new antibacterial agents. The study also highlights the synergy between cryo-electron microscopy and high-speed atomic force microscopy, demonstrating how combining these tools can unlock some elusive mysteries at the cellular level. Overall, the findings of this study advance our understanding of this essential biological phenomenon and pave the way for future research in this field.

***

Reference
DOI: 10.1038/s41467-025-60940-w

About Ritsumeikan University, Japan
Ritsumeikan University is one of the most prestigious private universities in Japan. Its main campus is in Kyoto, where inspiring settings await researchers. With an unwavering objective to generate social symbiotic values and emergent talents, it aims to emerge as a next-generation research-intensive university. It will enhance researcher potential by providing support best suited to the needs of young and leading researchers, according to their career stage. Ritsumeikan University also endeavors to build a global research network as a “knowledge node” and disseminate achievements internationally, thereby contributing to the resolution of social/humanistic issues through interdisciplinary research and social implementation.

Website: http://en.ritsumei.ac.jp/

Ritsumeikan University Research Report: https://www.ritsumei.ac.jp/research/radiant/eng/

About Professor Hiroyoshi Matsumura, from Ritsumeikan University, Japan
Professor Hiroyoshi Matsumura completed his Ph.D. in 2000 from the Graduate School of Engineering, University of Osaka, Japan. He is currently a Professor in the College of Life Sciences, Ritsumeikan University and a Ritsumeikan Advanced Research Academy (RARA) Associate Fellow. His expertise lies in various fields, including nano-bioscience, genome biology, molecular biology, structural biochemistry, and biophysics Prof. Matsumura has authored more than 200 research articles.

Funding information
This work was supported by: JSPS KAKENHI grant JP20K22630 (J.F.), JP23K06418 (R.U.), JP24K01994 (H.M.), JP24H02277 (H.M.), JP24H02270 (H.M.), JP23K18033 (H.M.), JP25H02292 (H.M.), JP24K0130 (T.U.); MEXT Promotion of Development of a Joint Usage/ Research System Project: Coalition of Universities for Research Excellence Program (CURE) (Grant Number JPMXP1323015482) (T.U.); Uehara Memorial Foundation (H.M.); Nagase Science and Technology Foundation (H.M.); The NOVARTIS Foundation (Japan) for the Promotion of Science (H.M.); Naito Science & Engineering Foundation (H.M.), G-7 Foundation (R.U.); JST OPERA (Open Innovation with Enterprises, Research Institute and Academia) grant JPMJOP1861 (K.N.); the Program for the R-GIRO Research from the Ritsumeikan Global Innovation Research Organization, Ritsumeikan University (H.M.); AMED BINDS (Platform Project for Supporting Drug Discovery and Life Science Research (BINDS)) grant JP21am0101117 and JP22ama121003 (K.N.), JP24ama121003 (K.N.), and JP23ama121001 (H.M.); AMED CiCLE (Cyclic Innovation for Clinical Empowerment) grant JP17pc0101020 (K.N.); JEOLYOKOGUSHI Research Alliance Laboratories of The University of Osaka (K.N.); the Cooperative Research Program of the Institute for Protein Research, The University of Osaka (CR-22-02 and CR-23-02).

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