Stacking Up: The Expanding Catalog of Filament-Forming Enzymes

Abstract Enzyme filamentation has emerged as a widespread and functionally important mode of macromolecular organization. Once viewed as an unusual property of a few metabolic enzymes, reversible filament formation is now known for more than 50 enzymes across bacteria, archaea, plants, fungi, and animals. This review summarizes recent progress in the field, expanding substantially on our 2019 analysis and incorporating more than 300 new publications. We survey the known filament-forming enzymes, their catalytic activities, biological contexts, filament architectures, and available structural information from X-ray crystallography, cryo-electron microscopy, and in cellulo imaging approaches. Filamenting enzymes span five major enzyme classes and function in metabolism, stress responses, signaling, replication, and host defense. In many cases, polymerization occurs at critical metabolic branch points and appears to regulate enzyme activity, allostery, substrate channeling, localization, or sequestration. Distinct filament geometries, including linear stacks, solenoidal coils, tubes, and rings, are associated with specific functional outcomes and cellular roles. We also highlight emerging in cellulo structural studies of enzyme filaments, summarizing the insights they provide into filament organization and cellular assembly when available. Together, these findings highlight enzyme filamentation as a common mode of macromolecular organization with consequences for structure, assembly, and function in diverse biological contexts.