1.C.127.1.1
Human Apolipooprotein A1, APOL1, a tripanolytic factor of 398 aas and 4 possible α-helical TMSs in a 1 + 2 + 1 TMS arrangement. Pore-formation has been demonstrated in planar bilayer membranes. APOL1 inserts into such bilayers at acidic pH to form pH-gated non-selective cation channels that open upon pH neutralization. This corresponds to the pH changes encountered during endocytic-recycling, suggesting that APOL1 forms a cytotoxic cation channel in the parasite plasma membrane. Pore-formation is blocked by the serum resistance-associated VSG protein, SRA. See family discussion for a published description of this protein (Thomson and Finkelstein 2015). APOL1 risk variants induce opening of the mitochondrial permeability transition pore (Carney 2019). Cation channel conductance and pH gating of the innate immunity factor APOL1 is governed by pore lining residues in the C-terminal domain (Schaub et al. 2020). Two residues in the C-terminal domain (CTD), tyrosine-351 and glutamate-355 influence pH gating properties, and a single residue, aspartate-348, determines both cation selectivity and pH gating. Thus, the predicted transmembrane region closest to the APOL1 C-terminus is the pore-lining segment of this channel-forming protein (Schaub et al. 2020).