TABLE 1.
Summary of the functional roles of different regions of the amyloid proteins shown in Figure 3.
| Protein | Residues/region | (Dys-)function | References |
| αSyn | |||
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| 1–14 | Membrane insertion | Cholak et al., 2020 | |
| 1–25 | Initial membrane binding | Fusco et al., 2014 | |
| Extreme N-terminus and region around Y39 | Chaperone binding | Burmann et al., 2020 | |
| 36–42 + 45–57 | Involved in liposome clustering | Doherty et al., 2020 | |
| 36–42 + 45–57 | Forms intra- and intermolecular interactions important for fibril formation | Doherty et al., 2020 | |
| 37–54 | Forms β-hairpin crucial for nucleation/oligomerization processes | Mirecka et al., 2014 | |
| C-terminal region (91–140) | Protects protein from aggregation by shielding NAC region and/or β-hairpin C-terminal truncation (109-140) results in faster aggregation | Hoyer et al., 2004; Hong et al., 2011; Yu et al., 2015; Stephens et al., 2019 | |
| C-terminal region (residues 110–140) | Binding to chaperone-like protein SERF accelerates aggregation | Falsone et al., 2012 | |
| C-terminal region (residue 125–129) | Dopamine binding drives off-pathway oligomer formation | Herrera et al., 2008 | |
| TDP-43 | |||
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| 3–183 | Interactions initiate homodimerization important for polymerization dependent splicing activity | Shiina et al., 2010; Afroz et al., 2017 | |
| 1–10 (especially Arg6, Val7, Thr8, and Glu9) | Mediates full-length TDP-43 oligomerization important for splicing activity and key to initiate aggregate formation | Zhang et al., 2013 | |
| RRM1 (104–176), especially residue I107, D105, L111, W113, Q134, G146, F147, F149, R171, K176, N179 [RRM2 (192–262)] | Binds TG-rich DNA and UG-rich RNA for function (e.g., splicing, translation control, transport). RRM2 shows lower binding affinity. | Lukavsky et al., 2013; Kuo et al., 2014 | |
| RRMI1 (residue F147 and F149) and residue 208–441 | Prevents aggregation by enhancing solubility when bound to single stranded RNA/DNA | Huang et al., 2013 | |
| RRM1 (residue F147 and F149) and 321–366 | Autoregulation of own protein expression by binding to its mRNA | Ayala et al., 2011 | |
| Residue 320–340, especially W334, W385, and W412 | Involved in liquid-liquid phase separation | Conicella et al., 2016; Sun and Chakrabartty, 2017; Li H.R. et al., 2018 | |
| Aβ | |||
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| N-terminal domain (residues 1–17) | Binding to cystatin C (cysteine protease inhibitor) | Sastre et al., 2004 | |
| Aβ40: central region (residues 25–29); part of the structured fibril core but solvent accessible | Disaggregase activity when binding Lipocalin-type Prostaglandin D synthase (L-PGDS) | Kannaian et al., 2019 | |
| Tau | |||
 |
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| 1–202 | Binding to plasma membrane | Brandt et al., 1995 | |
| N-terminal domain (1–150) interacts with proline rich domain (151–244) | Dimerization (head to tail), suggested to be the natural form for function and toxicity | Rosenberg et al., 2008 | |
| Residue 1–117 and 118–402 | Electrostatic interactions between these regions drive phase separation | Boyko et al., 2019 | |
| 114–193 (P-rich domain) and 198–278 (microtubule-binding domain) | Actin binding and promoting F-actin bundling and G-actin assembling | He et al., 2009 | |
| N-terminal domain, proline-rich region and MBD | Chaperone binding | Mok et al., 2018 | |
| Proline rich domain, MBD | Interaction and polymerization of tubulin | Barbier et al., 2019; Chen et al., 2019; McKibben and Rhoades, 2019 | |
| Proline rich domain and C-terminal domain | Main locations of phosphorylation sites, but can be found throughout the whole sequence | Liu et al., 2007 | |
| MBD (295–305) | β-hairpin formation that protects the aggregation prone 306–311 region | Chen et al., 2019 | |
| MBD (residue 275–280 and 306–311) and other regions | Heparin binding drives aggregation; MBD shows highest affinity to heparin | Sibille et al., 2006 | |
| β2m | |||
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| Residue 1–6 | Stabilization of native structure; accelerates aggregation when deleted | Esposito et al., 2000 | |
| A and G strand (I7A, V9A, and V93A) | Mutations drive fibril growth by destabilizing local tertiary structure and increasing dynamics | Jones et al., 2003b | |
| A, B, E, F strand (6–11, 21–28, 64–70, 79–83) | Interaction with chaperone αB-crystalline preventing oligomerization and fibril formation | Esposito et al., 2013 | |
| Orb2B | |||
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| RNA binding domain | Interaction with RNA facilitates long term memory formation | Krüttner et al., 2012 | |
| IAPP | |||
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| 1–19 | Membrane binding and disruption | Brender et al., 2008 | |
| 1–17 and/or 30–37 | Liquid-liquid phase separation | Pytowski et al., 2020 | |
| PrP | |||
 |
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| N-terminal region (residues 23–90) | Interaction with Tau | Han et al., 2006 | |
| N-terminal region (residue 23–89) | Interaction with αSyn fibrils facilitating αSyn cell-to-cell spreading | Aulić et al., 2017 | |
| Residues 95–110 | Receptor binding site for Aβ42-oligomers | Laurén et al., 2009 | |
| Hydrophobic region (residue 111–134) | Hydrophobically driven binding/insertion with anionic membranes, this interaction is important for (murine) PrP to gain C-terminal Proteinase K resistance and convert it to PrPSc | Wang et al., 2010b | |
| Octapeptide region in N-terminal domain | Increased numbers of octapeptides that bind Ca2+ promotes fibril formation and disease development | Goldfarb et al., 1991 | |
Each protein sequence is coloured, highlighting regions with different functional activity or those which have been mapped biochemically. RRM, RNA recognition motif; MBD, microtubule binding domain.