Preprint

PUBDB-2025-01837

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The many lives of a single sequence: Functional plasticity through amyloid polymorphism

Cali, M. P.CSSB*DESY* ; Monistrol, J.CSSB*DESY* ; Strati, F.CSSB*DESY* ; Schiller, J.CSSB*DESY* ; Indig, R. ; Markworth, R.CSSB*DESY* ; Landau, M. (Corresponding author)CSSB*EMBL*DESY*

2025

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Please use a persistent id in citations: doi:10.3204/PUBDB-2025-01837

Abstract: Amyloids play critical functional roles in biology, including microbial virulence, innate immunity, and cellular organization, broadening their traditional association with neurodegenerative and systemic diseases. This chapter explores the structural and functional plasticity of amyloids, emphasising how a single protein sequence can adopt multiple fibrillar conformations, termed polymorphs, each with distinct biological outcomes. We synthesise recent high-resolution structural insights from cryo-EM, NMR, and microcrystallography that elucidate the polymorphic behaviour of amyloids in both pathogenic and functional contexts. Particular focus is placed on bacterial functional amyloids that stabilise biofilms and modulate host-pathogen interactions, and on antimicrobial peptides that form reversible fibrils with cytotoxic or immune-stimulatory functions. We also highlight the emerging paradigm of amyloid–nucleic acid co-assemblies and their role in immune recognition, autoimmunity, and possibly the origin of life. By examining structure-function relationships across a broad evolutionary spectrum, we argue that amyloid polymorphism constitutes a general mechanism of biological regulation. Understanding how these fibrils shift between states, including cross-β, cross-α, nanotubular, or phase-separated condensates, offers profound insight into their dual roles in health and disease. This perspective repositions amyloids not merely as pathological end-products, but as versatile, ancient scaffolds for structural adaptation and functional innovation.

Note: Grants: Israel Science Foundation, Grant No. 2111/20 Cure Alzheimer's Fundthe Forschungskooperation Niedersachsen – Israel, Volkswagenstiftung, No: 76251-4659/2022 (ZN 4042)ERC, FuncAmyloid, 101087140PIER (PIF-2024-04) !!!

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Contributing Institute(s):

1. FPF Functional Protein Fibrils (CSSB-F)

Research Program(s):

1. 633 - Life Sciences – Building Blocks of Life: Structure and Function (POF4-633) (POF4-633)
2. FuncAmyloid - Structure, Function and Regulation of Antimicrobial and Virulent Amyloids at High-resolution (101087140) (101087140)

Experiment(s):

1. No specific instrument

Appears in the scientific report 2025

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Linked articles:

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Contribution to a book Pigozzi Cali, M.CSSB*DESY* ; Monistrol, J.CSSB*DESY* ; Strati, F.Extern*CSSB* ; Schiller, J.CSSB*XFEL.EU*EMBL*DESY* ; Indig, R. ; Markworth, R.CSSB*DESY* ; Landau, M. (Corresponding author)CSSB*EMBL*DESY*
The Many Lives of a Single Sequence: Functional Plasticity Through Amyloid Polymorphism
2026[Ebook] Fibrous Proteins: Structures and Mechanisms / Parry, David A. D. ; Luther, Pradeep K. 2nd ed. 2026, Cham : Springer Nature Switzerland, 2026, Cham : Springer Nature Switzerland, Subcellular Biochemistry 113, : 2nd ed. 2026, 521 - 558 (2026) [10.3204/PUBDB-2025-01867]2026     Files  Fulltext BibTeX | EndNote: XML, Text | RIS

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