The Importance of Being Imperfect: Structure and Function of Bacterial Amyloid

Amyloids, once viewed solely as pathological hallmarks, are now recognized as widespread and versatile functional protein assemblies. Bacterial functional amyloids (FuBAs), particularly curli (CsgA) from Escherichia coli and FapC from Pseudomonas, have emerged as paradigms for understanding amyloid structure, assembly, and function. The recent cryo-EM-based structure of FapC, together with others' combined cryo-EM and integrative computational studies on CsgA, reveal a β-solenoid fold stabilized by imperfect repeats, producing fibrils of exceptional stability and low polymorphism, whose biogenesis is tightly controlled through dedicated accessory factors, ensuring precise secretion and nucleation. FuBAs not only scaffold biofilms but also display intrinsic catalytic activity, expanding the biochemical repertoire of extracellular matrices. They also exhibit hierarchical mechanical properties ranging from GPa stiffness at the fibril core to kPa elasticity in hydrated biofilms. FuBA operons are phylogenetically widespread, with repeat variation contributing to sequence diversity and functional adaptability. FuBAs might be seen as evolutionary intermediates between disordered peptides with significant self-interaction tendencies and highly structured globular proteins. Their simple structures make them robust platforms for biomaterial engineering. Understanding the interplay between sequence repeats, fibril architecture, and emergent functions opens avenues for harnessing amyloids as programmable nanomaterials with applications in catalysis, synthetic biology, and biofilm control.