Recent cryo-EM structures redefine the functional amyloid landscape
Salvador Ventura1, Andrea Bartolomé-Nafría2, Javier Garcia-Pardo2
1Departament de Bioquímica i Biologia Molecular, Institut de Biotecnologia i de Biomedicina (IBB), Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; Institut d'Investigació i Innovació Parc Taulí (I3PT-CERCA), Hospital Universitari Parc Taulí, Universitat Autònoma de Barcelona, Sabadell, Spain.
Progress in Molecular Biology and Translational Science
|July 16, 2026
Summary
Functional amyloids, crucial for biological processes, are revealed through advanced cryogenic electron microscopy (cryo-EM) structures. These studies show how the amyloid fold enables diverse physiological functions, distinct from disease-related amyloids.
Area of Science:
- Structural Biology
- Molecular Biology
- Biophysics
Background:
- Amyloids are traditionally linked to diseases but also perform vital physiological roles.
- Recent advances in cryogenic electron microscopy (cryo-EM) have enabled high-resolution structural studies of functional amyloids.
- Understanding the structural basis of functional amyloids is key to deciphering their biological roles.
Purpose of the Study:
- To review and synthesize recent structural insights into functional amyloids.
- To highlight how the amyloid fold is repurposed for diverse biological activities.
- To compare structural principles across different functional amyloids.
Main Methods:
- Cryogenic electron microscopy (cryo-EM) for high-resolution structural determination.
- Analysis of atomic structures of various functional amyloids, including Orb2, hnRNPDL-2, PMEL, and FapC.
- Comparative structural analysis to identify shared principles and organism-specific adaptations.
Main Results:
- The first atomic structure of the neuronal amyloid Orb2, essential for memory, was determined.
- Structures of human RNA-binding proteins like hnRNPDL-2 revealed amyloid assembly for RNA metabolism.
- Cryo-EM structures of PMEL and bacterial FapC elucidated roles in pigmentation and biofilm formation, respectively.
- Shared structural principles underlying functional amyloid formation were identified across different organisms.
Conclusions:
- The amyloid fold is a versatile structural motif repurposed for essential physiological functions.
- Cryo-EM has revolutionized the study of functional amyloids, revealing their atomic structures and mechanisms.
- Functional amyloids exhibit conserved and unique structural features that differentiate them from pathological amyloids.
