Table 2 Predicted effects of mutations in ETC subunits
From: Mitochondrial mutations and metabolic adaptation in pancreatic cancer
ETC subunit | PDCL | Mutation | Predicted effect |
|---|---|---|---|
Complex I human residues (corresponding Thermus thermophilus residues) | |||
ND5 | TKCC-02 | Frameshift | Part of ND5 loss, therefore no active complex I |
| Â | TKCC-07 | V132A (V119) | V sits at the end of TM4 and faces TM3, may slightly destabilise fold in this area. |
| Â | TKCC-07 | A415T (V409) | A sits on TM13, facing TMs 9 and 10, may de-stabilise fold in this area and/or make channel cavity leaky in this area. |
| Â | TKCC-26-LO | D58N (F55) | D sits on the beta-sheet from the beta-H motif, may interfere with conformational coupling. |
ND4 | TKCC-07 | M201T (L199) | M sits on key flexible helix 7 and faces the lipid or supernumerary subunit, may interfere with mechanics of TM7 and decrease NADH:Q oxidoreductase activity and/or proton pumping. |
ND2 | TKCC-07 | G168S (A247) | Directly facing traverse helix HL from ND5, might decrease NADH:Q oxidoreductase activity (or proton pumping only) preventing full movement of HL. |
| Â | TKCC-15-LO | W30S (L108) | W provides part of a seal between ND2 and ND4L, therefore mutation might make it somewhat leaky to protons. |
ND6 | TKCC-07 | T156I (V142) | T is near key ND2 Glu34 (GluTM5), so the mutation may interfere with its pKa and so with proton pumping through ND2. Fold in this area will also be disturbed. |
Complex III (bovine model 2FYU) | |||
CytB subunit | TKCC-03 | M316Δ | May interfere with fold at the junction with subunit 6. |
| Â | TKCC-04 | M376T | Leu in bovine- peripheral, but may interact with N-term helix from subunit 7. |
| Â | TKCC-18-LO | E271K | E in bovine- close to heme (6 A, directly facing the edge), so may well interfere with its redox properties. |