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

## TL;DR

Bacterial amyloids like CsgA and FapC have unique structures and functions, offering potential for biomaterials and biofilm control.

## Contribution

The paper reveals the β-solenoid structure of FapC and its role in amyloid stability and function.

## Key findings

- FuBAs have a β-solenoid fold stabilized by imperfect repeats, leading to stable and low polymorphic fibrils.
- FuBAs exhibit mechanical properties from GPa stiffness to kPa elasticity and intrinsic catalytic activity.
- FuBA operons are phylogenetically widespread, with repeat variation enabling functional adaptability.

## Abstract

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.

Functional bacterial amyloids such as CsgA and FapC have been widely studied to understand the relationship between aggregation and function. The recently solved structure of FapC reveals a Greek‐key motif in which extensive hydrogen bonding and packing interactions formed by residues in conserved imperfect repeats stabilize a β‐solenoid core. FuBA fibrils display impressive mechanical and catalytic properties and are a very promising scaffold for the development of new biomaterials.