The Structure and Dynamics of Higher-Order Assemblies: Amyloids, Signalosomes, and Granules

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2016 May 21

PMID 27203110

Citations 178

Authors

Hao Wu

Monika Fuxreiter

Affiliations

Soon will be listed here.

Abstract

We here attempt to achieve an integrated understanding of the structure and dynamics of a number of higher-order assemblies, including amyloids, various kinds of signalosomes, and cellular granules. We propose that the synergy between folded domains, linear motifs, and intrinsically disordered regions regulates the formation and intrinsic fuzziness of all higher-order assemblies, creating a structural and dynamic continuum. We describe how such regulatory mechanisms could be influenced under pathological conditions.

Citing Articles

Toward universal models for collective interactions in biomolecular condensates.

Milanetti E, Manjunatha K, Ruocco G, Maritan A, Fuxreiter M Biophys Rev (Melville). 2025; 6(1):011401.

PMID: 40060928 PMC: 11890157. DOI: 10.1063/5.0244227.

Context-Dependent Heterotypic Assemblies of Intrinsically Disordered Peptides.

Qiao Y, Zia A, Wu G, Liu Z, Guo J, Chu M J Am Chem Soc. 2025; 147(4):2978-2983.

PMID: 39808585 PMC: 11841035. DOI: 10.1021/jacs.4c12150.

Cellular Function of a Biomolecular Condensate Is Determined by Its Ultrastructure.

Scholl D, Boyd T, Latham A, Salazar A, Khan A, Boeynaems S bioRxiv. 2025; .

PMID: 39763716 PMC: 11703246. DOI: 10.1101/2024.12.27.630454.

Emerging regulatory mechanisms and functions of biomolecular condensates: implications for therapeutic targets.

Jeon S, Jeon Y, Lim J, Kim Y, Cha B, Kim W Signal Transduct Target Ther. 2025; 10(1):4.

PMID: 39757214 PMC: 11701242. DOI: 10.1038/s41392-024-02070-1.

Binding site maturation modulated by molecular density underlies Ndc80 binding to kinetochore receptor CENP-T.

Tarasovetc E, Sissoko G, Maiorov A, Mukhina A, Ataullakhanov F, Cheeseman I Proc Natl Acad Sci U S A. 2024; 121(52):e2401344121.

PMID: 39700145 PMC: 11670232. DOI: 10.1073/pnas.2401344121.

References

Murakami T, Qamar S, Lin J, Kaminski Schierle G, Rees E, Miyashita A . ALS/FTD Mutation-Induced Phase Transition of FUS Liquid Droplets and Reversible Hydrogels into Irreversible Hydrogels Impairs RNP Granule Function. Neuron. 2015; 88(4):678-90. PMC: 4660210. DOI: 10.1016/j.neuron.2015.10.030. View

Frederick K, Debelouchina G, Kayatekin C, Dorminy T, Jacavone A, Griffin R . Distinct prion strains are defined by amyloid core structure and chaperone binding site dynamics. Chem Biol. 2014; 21(2):295-305. PMC: 4030713. DOI: 10.1016/j.chembiol.2013.12.013. View

Fowler D, Koulov A, Alory-Jost C, Marks M, Balch W, Kelly J . Functional amyloid formation within mammalian tissue. PLoS Biol. 2005; 4(1):e6. PMC: 1288039. DOI: 10.1371/journal.pbio.0040006. View

Kwon I, Kato M, Xiang S, Wu L, Theodoropoulos P, Mirzaei H . Phosphorylation-regulated binding of RNA polymerase II to fibrous polymers of low-complexity domains. Cell. 2013; 155(5):1049-1060. PMC: 4010232. DOI: 10.1016/j.cell.2013.10.033. View

Baroja-Mazo A, Martin-Sanchez F, Gomez A, Martinez C, Amores-Iniesta J, Compan V . The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response. Nat Immunol. 2014; 15(8):738-48. DOI: 10.1038/ni.2919. View

Cai X, Chen J, Xu H, Liu S, Jiang Q, Halfmann R . Prion-like polymerization underlies signal transduction in antiviral immune defense and inflammasome activation. Cell. 2014; 156(6):1207-1222. PMC: 4034535. DOI: 10.1016/j.cell.2014.01.063. View

Tompa P . Structural disorder in amyloid fibrils: its implication in dynamic interactions of proteins. FEBS J. 2009; 276(19):5406-15. DOI: 10.1111/j.1742-4658.2009.07250.x. View

Yin Q, Lin S, Lamothe B, Lu M, Lo Y, Hura G . E2 interaction and dimerization in the crystal structure of TRAF6. Nat Struct Mol Biol. 2009; 16(6):658-66. PMC: 2834951. DOI: 10.1038/nsmb.1605. View

Tradewell M, Yu Z, Tibshirani M, Boulanger M, Durham H, Richard S . Arginine methylation by PRMT1 regulates nuclear-cytoplasmic localization and toxicity of FUS/TLS harbouring ALS-linked mutations. Hum Mol Genet. 2011; 21(1):136-49. DOI: 10.1093/hmg/ddr448. View

10.

Altmeyer M, Neelsen K, Teloni F, Pozdnyakova I, Pellegrino S, Grofte M . Liquid demixing of intrinsically disordered proteins is seeded by poly(ADP-ribose). Nat Commun. 2015; 6:8088. PMC: 4560800. DOI: 10.1038/ncomms9088. View

11.

Jain S, Parker R . The discovery and analysis of P Bodies. Adv Exp Med Biol. 2012; 768:23-43. DOI: 10.1007/978-1-4614-5107-5_3. View

12.

Hyman A, Weber C, Julicher F . Liquid-liquid phase separation in biology. Annu Rev Cell Dev Biol. 2014; 30:39-58. DOI: 10.1146/annurev-cellbio-100913-013325. View

13.

Tanaka M, Chien P, Naber N, Cooke R, Weissman J . Conformational variations in an infectious protein determine prion strain differences. Nature. 2004; 428(6980):323-8. DOI: 10.1038/nature02392. View

14.

Wasmer C, Schutz A, Loquet A, Buhtz C, Greenwald J, Riek R . The molecular organization of the fungal prion HET-s in its amyloid form. J Mol Biol. 2009; 394(1):119-27. DOI: 10.1016/j.jmb.2009.09.015. View

15.

Wu H . Higher-order assemblies in a new paradigm of signal transduction. Cell. 2013; 153(2):287-92. PMC: 3687143. DOI: 10.1016/j.cell.2013.03.013. View

16.

Qiao Q, Yang C, Zheng C, Fontan L, David L, Yu X . Structural architecture of the CARMA1/Bcl10/MALT1 signalosome: nucleation-induced filamentous assembly. Mol Cell. 2013; 51(6):766-79. PMC: 3929958. DOI: 10.1016/j.molcel.2013.08.032. View

17.

Chen T, Song J, Chan H . Theoretical perspectives on nonnative interactions and intrinsic disorder in protein folding and binding. Curr Opin Struct Biol. 2014; 30:32-42. DOI: 10.1016/j.sbi.2014.12.002. View

18.

Alberti S, Halfmann R, King O, Kapila A, Lindquist S . A systematic survey identifies prions and illuminates sequence features of prionogenic proteins. Cell. 2009; 137(1):146-58. PMC: 2683788. DOI: 10.1016/j.cell.2009.02.044. View

19.

Balagopalan L, Kortum R, Coussens N, Barr V, Samelson L . The linker for activation of T cells (LAT) signaling hub: from signaling complexes to microclusters. J Biol Chem. 2015; 290(44):26422-9. PMC: 4646300. DOI: 10.1074/jbc.R115.665869. View

20.

Wright P, Dyson H . Intrinsically disordered proteins in cellular signalling and regulation. Nat Rev Mol Cell Biol. 2014; 16(1):18-29. PMC: 4405151. DOI: 10.1038/nrm3920. View