On the Structural Diversity and Individuality of Polymorphic Amyloid Protein Assemblies. Issue 20 (1st October 2021)

• Record Type: Journal Article
• Authors: Lutter, Liisa; Aubrey, Liam D.; Xue, Wei-Feng
• Is Part Of: Journal of molecular biology. Volume 433:Issue 20(2021)
• Publication Date: 2021-10-01
• Subjects: amyloid -- fibril structure -- polymorphism -- folding/misfolding -- protein aggregation; 3D three-dimensional -- Å ångström -- AD Alzheimer's disease -- AFM atomic force microscopy -- AI artificial intelligence -- AL amyloid light chain -- Aβ40 amyloid β peptide fragment, amino acid residues 1-40 -- Aβ42 amyloid β protein fragment, amino acid residues 1-42 -- CASP Critical Assessment of protein Structure Prediction -- CASP14 14th Community Wide Experiment on the Critical Assessment of Techniques for Protein Structure Prediction -- CBD corticobasal degeneration -- Cryo-EM cryogenic electron microscopy -- dGAE tau protein fragment, amino acid residues 297-391 -- EM electron microscopy -- EMDB The Electron Microscopy Data Bank -- IAPP islet amyloid polypeptide -- microED microcrystal electron diffraction -- PDB The Protein Data Bank -- PTMs post-translational modifications -- RCSB Research Collaboratory for Structural Bioinformatics -- ssNMR solid-state nuclear magnetic resonance; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2021.167124
• Languages: English
• ISSNs: 0022-2836

Abstract

Graphical abstract: Highlights: A single polypeptide sequence may assemble into many different amyloid fibril structures. Due to this polymorphism, prediction of amyloid structures from amino acid sequence is far from being resolved. Structural data of amyloid in the PDB and the EMDB (up to March 2021) are summarised. Cryo-EM and ssNMR have revealed extensive structural diversity of the cross-β amyloid core architecture. AFM has revealed the individuality displayed by each fibril structure in heterogeneous amyloid populations. Abstract: The prediction of highly ordered three-dimensional structures of amyloid protein fibrils from the amino acid sequences of their monomeric self-assembly precursors constitutes a challenging and unresolved aspect of the classical protein folding problem. Because of the polymorphic nature of amyloid assembly whereby polypeptide chains of identical amino acid sequences under identical conditions are capable of self-assembly into a spectrum of different fibril structures, the prediction of amyloid structures from an amino acid sequence requires a detailed and holistic understanding of its assembly free energy landscape. The full extent of the structure space accessible to the cross-β molecular architecture of amyloid must also be resolved. Here, we review the current understanding of the diversity and the individuality of amyloid structures, and how the polymorphic landscape of amyloid links to biology and disease phenotypes. We present a comprehensive review of structural models of amyloid fibrils derived by cryo-EM, ssNMR and AFM to date, and discuss the challenges ahead for resolving the structural basis and the biological consequences of polymorphic amyloid assemblies.