Aggregation and interaction regions in monomeric soluble proteins.

<p>In panels A–D, aggregation-prone residues at less and more than 3 Å from interaction sites are shown in red and green, respectively. Interface residues not included in aggregation-prone regions are shown in dark blue. Rest of residues are shown in light blue. In all panels the predicted interaction surface is used for calculation. A) Human myoglobin (PDB ID: 4MBN). B) Maltose Binding Protein (MBP) (PDB ID: 4MBP). C) Human thioredoxin (TRX) (PDB ID: 3TRX). Gatekeeper residues are shown in purple and active cysteines in yellow. D) Same orientation that in C, Human TRX in a mixed disulfide intermediate complex with a peptide from the transcription factor NF kappa B (PDB ID: 1MDI). E) Ribbon representation of human ubiquitin (PDB ID: 1UBQ). Aggregation-prone secondary structures near the interface are shown in red. Basic residues in the vicinity of aggregation-prone regions are shown in purple. F) Same orientation than E). Complex of human ubiquitin with a CUE ubiquitin binding domain (PDB ID: 1OTR).</p

Aggregation and interaction regions in human immunoglobulins.

<p>In all panels, immunoglobulin (Ig) aggregation-prone residues at less and more than 3 Å from interaction sites are shown in red and green, respectively. Interface residues not included in aggregation-prone regions are shown in dark blue. Rest of residues are shown in light blue. A) The interface in the native structure of Ig light chain variable domain (LC) is used for calculation (PDB ID: 2Q20). B) Native homodimer of Ig LC, the second monomer is shown in yellow. C) The interface in the native structure of IgG heterotetramer is used for calculation and the Ig heavy chain (HC) represented (PDB ID: 1HZH). D) Native IgG heterotetramer. Ig LCs and the second Ig HC are indicated.</p

Comparison of aggregation predictions and experimental available data for human globular proteins and proximity of aggregation-prone regions to predicted and real interfaces.

1<p>Percentage of residues in the aggregation-prone region at less than 3 Å from a protein predicted interaction residue.</p>2<p>Percentage of residues in the aggregation-prone region at less than 3 Å from a residue located at the interface of the following complexes: β2-microglubulin in complex with HLA heavy chain [1DUZ] and with HFE [1A6Z]. Native tetrameric structure of transthyretin (PDB code 1TTA). Dimeric structure of SOD1 (PDB code 2C9V). Lysozyme in complex with a camelid antibody (PDB code 1OP9). Dimeric structure of Immunoglobulin LC variable domain (PDB code 2Q20). HCs and LCs of a IgG1 human immunoglobulin (PDB code 1HZH).</p>1,2<p>In brackets the percentage of residues in the aggregation-prone region close to a random surface of the same size than the considered interface.</p

Interface Proximity Index (IPI) of aggregation-prone regions in human globular amyloidogenic proteins.

<p>Aggregation-prone regions are coloured according to their IPI values (see the scale). A) β2-microglobulin, B) transthyretin, C) immunoglobulin G heavy chain, D) SOD1 and E) immunoglobulin light chain variable domain.</p

Aggregation-prone regions at the interface of selected homodimeric eukaryotic proteins.

<p>Aggregation-prone regions in which more than 85% of the residues are at less than 3 Å from the interface are highlighted in green. The PDB ID is indicated for each dimer (see also <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000476#pcbi-1000476-t002" target="_blank">Table 2</a>).</p

New interfaces at human lysozyme and Aß peptide aggregation-prone regions.

<p>In all panels, aggregation-prone residues at less and more than 3 Å from interaction sites are shown in red and green, respectively. Interface residues not included in aggregation-prone regions are shown in dark blue. Rest of residues are shown in light blue. A) The predicted interaction surface of lysozyme is used for calculation. B) The interface between lysozyme and a camelid antibody is used for calculation (PDB ID: 1OP9). C) Lysozyme complex with a camelid antibody. D) Ribbon representation of Aß peptide. The interface between the peptide and a designed affibody is used for calculation (PDB ID: 2OTK). E) Aß peptide bound to a designed affibody.</p

Aggregation and interaction regions in human transthyretin.

<p>In all panels, transthyretin (TTR) aggregation-prone residues at less and more than 3 Å from interaction sites are shown in red and green, respectively. Interface residues not included in aggregation-prone regions are shown in dark blue. Rest of residues are shown in light blue. A) The predicted interaction surface of a TTR monomer is used for calculation. B) The interface in the native tetrameric structure of TTR is used for calculation (PDB ID:1TTA). C) Dimer of TTR. D) TTR native tetrameric structure. The first dimer is twisted 90° relative to C, the second one is shown in yellow.</p

Aggregation and interaction regions in human SOD1.

<p>In panels A, B and C SOD1 aggregation-prone residues at less and more than 3 Å from interaction sites are shown in red and green, respectively. Interface residues not included in aggregation-prone regions are shown in dark blue. Rest of residues are shown in light blue. A) The predicted interaction surface of a SOD1 monomer is used for calculation. B) The interface in the native dimeric structure of SOD1 is used for calculation (PDB ID:2C9V). C) Native dimer of SOD1, the second monomer is shown in yellow. D) Ribbon representation of the SOD1 dimer, predicted aggregation-prone regions are shown in red.</p

The inner membrane contains proteins with different number of transmembrane segments and associated aggregation propensities.

<p>Diagram of the inner membrane protein set showing the Na4vSS value and the number of transmembrane segments.</p

Comparison between cytosolic proteins theoretical expression levels and their aggregation parameters.

<p>A) Cumulative distributions of Na4vSS values in the 10% cytosolic proteins with the highest (black) and lowest (grey) Codon Adaptation Index (CAI) values. B) Correlation between the CAI and the Na4vSS values. Each point represents the average value over all the sequences having a CAI value comprised in an interval of 0.03.</p