| Domain/Feature | Description | Function |
|---|---|---|
| Transmembrane helix (anchor) | Single N-terminal transmembrane α-helix that anchors ISP-1 in the mitochondrial inner membrane as a core subunit of Complex III/cytochrome bc1. The membrane anchor remains relatively static while the catalytic domain moves. (pqac-00000007, pqac-00000011, pqac-00000028, pqac-00000029) | Positions ISP-1 within Complex III and maintains the spatial framework needed for electron transfer between quinol oxidation and cytochrome c1 reduction. (pqac-00000007, pqac-00000029) |
| Tether domain (spring mechanism) | Flexible linker connecting the membrane anchor to the extrinsic catalytic head. In mechanistic models it behaves as a chemical “spring,” alternating between extended and relaxed/helical conformations during catalysis; the qm150 Pro→Ser mutation lies in this region. (pqac-00000007, pqac-00000008, pqac-00000028, pqac-00000040, pqac-00000041) | Enables controlled movement of the head domain between the Qo site and cytochrome c1, thereby regulating enzyme-substrate complex formation, electron flux through the Q-cycle, and ROS propensity. (pqac-00000008, pqac-00000040, pqac-00000041) |
| Head domain with 2Fe-2S cluster | Extrinsic/mobile catalytic head domain containing the Rieske 2Fe-2S cluster with distinctive histidine coordination and relatively high redox potential. This domain projects to the P side/intermembrane-space side of the membrane. (pqac-00000007, pqac-00000009, pqac-00000028) | Accepts an electron from ubiquinol at the Qo site and later donates that electron to heme c1; its mobility and redox chemistry are central to Complex III catalysis. (pqac-00000000, pqac-00000008, pqac-00000009) |
| Qo site interaction | ISP-1 docks at the quinol oxidation (Qo) site near cytochrome b, where oxidized ISP interacts with ubiquinol (QH2). The first electron-transfer step reduces the 2Fe-2S cluster and generates a semiquinone intermediate. (pqac-00000001, pqac-00000003, pqac-00000008, pqac-00000030) | Executes the initial oxidation of QH2 and bifurcates electron flow in the Q-cycle, a key energy-conserving step in Complex III. (pqac-00000001, pqac-00000003, pqac-00000010) |
| Cytochrome c1 interaction | After reduction at the Qo site, the ISP-1 head swings toward cytochrome c1 into the c1-state conformation, where the reduced 2Fe-2S center transfers its electron to heme c1. (pqac-00000000, pqac-00000008, pqac-00000011, pqac-00000014) | Couples quinol oxidation to reduction of cytochrome c1 and ultimately cytochrome c, supporting downstream electron flow to Complex IV. (pqac-00000000, pqac-00000011) |
| Proton-exiting gate role | Experimental disruption of the Rieske 2Fe-2S center creates a proton leak, supporting the model that the cluster/head region acts as a proton-exiting gate in cytochrome bc1. (pqac-00000010, pqac-00000012) | Prevents nonspecific proton leakage and helps couple electron transfer to proton translocation, preserving the proton motive force used for ATP synthesis. (pqac-00000010, pqac-00000012) |
| Overall Q-cycle reaction (EC 7.1.1.8; ubiquinol:ferricytochrome-c reductase) | ISP-1 is a catalytic subunit of Complex III/ubiquinol:cytochrome c oxidoreductase. In the Q-cycle, it transfers electrons from ubiquinol to cytochrome c1 while coordinating with the Qo and Qi sites to couple redox chemistry to proton translocation across the inner membrane. (pqac-00000000, pqac-00000001, pqac-00000010, pqac-00000029) | Contributes to the net reaction of ubiquinol oxidation and cytochrome c reduction while generating the proton gradient required for oxidative phosphorylation and ATP production. (pqac-00000000, pqac-00000001, pqac-00000029) |


*Table: This table summarizes the major structural features of the C. elegans ISP-1/Rieske iron-sulfur protein and links each feature to its role in Complex III catalysis. It is useful for connecting protein architecture to the Q-cycle mechanism and the gene’s primary biochemical function.*