On the Structural Diversity and Individuality of Polymorphic Amyloid Protein Assemblies |
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Affiliation: | 1. Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK |
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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. |
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Keywords: | amyloid fibril structure polymorphism folding/misfolding protein aggregation 3D" },{" #name" :" keyword" ," $" :{" id" :" k0035" }," $$" :[{" #name" :" text" ," _" :" three-dimensional Å" },{" #name" :" keyword" ," $" :{" id" :" k0045" }," $$" :[{" #name" :" text" ," _" :" ångström AD" },{" #name" :" keyword" ," $" :{" id" :" k0055" }," $$" :[{" #name" :" text" ," _" :" Alzheimer’s disease AFM" },{" #name" :" keyword" ," $" :{" id" :" k0065" }," $$" :[{" #name" :" text" ," _" :" atomic force microscopy AI" },{" #name" :" keyword" ," $" :{" id" :" k0075" }," $$" :[{" #name" :" text" ," _" :" artificial intelligence AL" },{" #name" :" keyword" ," $" :{" id" :" k0085" }," $$" :[{" #name" :" text" ," _" :" amyloid light chain amyloid β peptide fragment, amino acid residues 1-40 amyloid β protein fragment, amino acid residues 1-42 CASP" },{" #name" :" keyword" ," $" :{" id" :" k0115" }," $$" :[{" #name" :" text" ," _" :" Critical Assessment of protein Structure Prediction CASP14" },{" #name" :" keyword" ," $" :{" id" :" k0125" }," $$" :[{" #name" :" text" ," _" :" 14th Community Wide Experiment on the Critical Assessment of Techniques for Protein Structure Prediction CBD" },{" #name" :" keyword" ," $" :{" id" :" k0135" }," $$" :[{" #name" :" text" ," _" :" corticobasal degeneration Cryo-EM" },{" #name" :" keyword" ," $" :{" id" :" k0145" }," $$" :[{" #name" :" text" ," _" :" cryogenic electron microscopy dGAE" },{" #name" :" keyword" ," $" :{" id" :" k0155" }," $$" :[{" #name" :" text" ," _" :" tau protein fragment, amino acid residues 297-391 EM" },{" #name" :" keyword" ," $" :{" id" :" k0165" }," $$" :[{" #name" :" text" ," _" :" electron microscopy EMDB" },{" #name" :" keyword" ," $" :{" id" :" k0175" }," $$" :[{" #name" :" text" ," _" :" The Electron Microscopy Data Bank IAPP" },{" #name" :" keyword" ," $" :{" id" :" k0185" }," $$" :[{" #name" :" text" ," _" :" islet amyloid polypeptide microED" },{" #name" :" keyword" ," $" :{" id" :" k0195" }," $$" :[{" #name" :" text" ," _" :" microcrystal electron diffraction PDB" },{" #name" :" keyword" ," $" :{" id" :" k0205" }," $$" :[{" #name" :" text" ," _" :" The Protein Data Bank PTMs" },{" #name" :" keyword" ," $" :{" id" :" k0215" }," $$" :[{" #name" :" text" ," _" :" post-translational modifications RCSB" },{" #name" :" keyword" ," $" :{" id" :" k0225" }," $$" :[{" #name" :" text" ," _" :" Research Collaboratory for Structural Bioinformatics ssNMR" },{" #name" :" keyword" ," $" :{" id" :" k0235" }," $$" :[{" #name" :" text" ," _" :" solid-state nuclear magnetic resonance |
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