Fig 1.
The database construction of MTSviewer, from initial mitochondrial databases to data integration and visualization.
Fig 2.
A sample output from MTSviewer investigating human PINK1, a mitochondrial kinase with a uniquely long MTS and multiple predicted cleavage sites. Protein sequence, prediction algorithms, and N-terminomics data tables have been omitted for clarity but are available in full on the interactive MTSviewer web server. Ser73Leu has been highlighted as a variant of interest, as Ser73 is found within a region of high MTS propensity near the predicted MitoFates cleavage site.
Fig 3.
Global analysis of per-residue iMLP and pLDDT scores across the human mitochondrial proteome.
AlphaFold pLDDT and iMLP scores were extracted on a per-residue basis (426832 residues total) for all 1136 proteins in the human mitochondrial proteome and were visualized as a kernel density estimate (KDE) plot using the seaborn library in Python. Two density plots were generated and merged to visualize low density datapoints—one for all pLDDT and iMLP scores (blue), and one for residues with high MTS propensity (iMLP score > 3) (red). Based on the KDE plot, data were grouped into three subsets (Cluster 1: pLDDT 80–100, iMLP > 3, Cluster 2: pLDDT 25–50, iMLP > 3, and Cluster 3: pLDDT 80–100, iMLP < 1.5) and the % distance of each residue within their corresponding protein length were calculated and written as the average % distance from N-terminus ± standard deviation for all residues in that cluster.
Fig 4.
Structural visualization of human KMO and PUSL1 iMTS propensity via MTSviewer.
AlphaFold models of KMO (Uniprot: O15229) and PUSL1 (Uniprot: Q8N0Z8) colored by iMLP score within MTSviewer. MTS’s are annotated as blue rectangles on the sequence schematics. The C-MTS of KMO is predicted as helical, solvent-accessible, and is distinct from the folded domain of KMO. Arg452 is highlighted as a variant of interest (Arg452Cys). PUSL1 contains a putative N-MTS and two iMTS’s (denoted iMTS-1 and iMTS-2), which are both found within the folded domain and would likely be inaccessible for TOM70 binding in this mature state.