The amyloid packing difference: A pairwise comparison metric for amyloid structures
- 1Medical Research Council Laboratory of Molecular Biology, CB2 0QH Cambridge, UK. Electronic address: [email protected]
Abstract
Because a given protein may adopt different amyloid protofilament folds, it has become necessary to compare pairs of amyloid structures of a given protein. This article describes the amyloid packing difference (APD), which quantifies the difference between amyloid structures as the percentage of residues involved in unique cross-β packing interactions or side-chain orientations. Clustering of α-synuclein folds on APD values recapitulates clustering based on structural superpositions. Known protofilament folds of the prion protein, tau, α-synuclein, TDP-43, or TAF15 from different neurodegenerative diseases have APD values above 20%, whereas structures that have been associated with the same disease have APD values below 40%. Different individuals with peripheral amyloidosis have antibody light-chain structures with APDs above 60%, whereas transthyretin filaments are strikingly similar, with APDs below 25%. These observations provide context for the interpretation of APD values in future structure comparisons.
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BibTeX
@article{scheres2026amyloid,
title = {{The amyloid packing difference: A pairwise comparison metric for amyloid structures}},
author = {Sjors H. W. Scheres},
journal = {Structure},
year = {2026},
month = may,
doi = {10.1016/j.str.2026.04.014},
url = {https://doi.org/10.1016/j.str.2026.04.014},
note = {CC BY},
}
RIS
TY - JOUR
TI - The amyloid packing difference: A pairwise comparison metric for amyloid structures
AU - Sjors H. W. Scheres
PY - 2026
DA - 2026/05/22
JO - Structure
DO - 10.1016/j.str.2026.04.014
UR - https://doi.org/10.1016/j.str.2026.04.014
AB - Because a given protein may adopt different amyloid protofilament folds, it has become necessary to compare pairs of amyloid structures of a given protein. This article describes the amyloid packing difference (APD), which quantifies the difference between amyloid structures as the percentage of residues involved in unique cross-β packing interactions or side-chain orientations. Clustering of α-synuclein folds on APD values recapitulates clustering based on structural superpositions. Known protofilament folds of the prion protein, tau, α-synuclein, TDP-43, or TAF15 from different neurodegenerative diseases have APD values above 20%, whereas structures that have been associated with the same disease have APD values below 40%. Different individuals with peripheral amyloidosis have antibody light-chain structures with APDs above 60%, whereas transthyretin filaments are strikingly similar, with APDs below 25%. These observations provide context for the interpretation of APD values in future structure comparisons.
SN - 0969-2126
SN - 1878-4186
ER -