The table comparing amino acid sequences of various A P O L proteins. The table has 12 rows and 3 columns. The columns are labeled with helix 1, loop, and helix 2. Each row represents a different A P O L protein variant, including A P O L 1, A P O L 2, m A P O L 8, m A P O L 7, A P O L 3, A P O L 4, m A P O L 10, m A P O L 11, A P O L 5, A P O L 6, m A P O L 6, and m A P O L 9. Identical or similar amino acids shared between most A P O L s are highlighted in gray. Positively charged amino acids are colored red. In A P O L 1, N 264 is highlighted in blue. Amino acids defining a consensus sequence for interaction with cholesterol are highlighted in yellow. Amino acids essential for interaction with the antifibrotic drug 12-deoxyphorbol-13-palmitate are highlighted in green. The M A D domain is rich in cysteines and aromatic residues, which are colored light blue.
The APOL membrane-addressing domain. Identical or similar amino acids shared between most APOLs are highlighted in grey. Despite sequence divergence with other MAD isoforms, the (m)APOL6 and mAPOL9 MADs can also be structured in a double-stranded hairpin helix. Probable calmodulin-binding sites (http://calcium.uhnres.utoronto.ca/ctdb/ctdb/sequence.html), which also interact with phosphoinositides or cardiolipin (67, 68, 69), are underlined. Positively charged amino acids potentially involved in phospholipid interactions are colored red. In APOL1, N264, highlighted in blue, is essential for the cytotoxic activity of C-terminal APOL1 variants (65, 66). The amino acids highlighted in yellow define a consensus sequence for interaction with cholesterol (62). The amino acids highlighted in green are essential for interaction with the antifibrotic drug 12-deoxyphorbol-13-palmitate (59). Of note, the MAD domain is rich in cysteines (C) and/or aromatic residues (F, Y, and W), especially in the first half of the second helix (colored light blue). MAD, membrane-addressing domain.