Extended Data Figure 8. Structural and functional annotation of TAX-4.

a, Amino acid sequence alignment of TAX-4 with human CNG channel subunits and TAX-2, a CNGB subunit in C. elegans. Secondary structures and selected functionally important amino acids are annotated for TAX-4. The selectivity filter is boxed in blue, and S4 positive charges are colored in blue. Residues boxed in purple are involved in ion-pair interactions between S4 and S2-S3. Residues boxed in red in S6 and the pore helix interact with residues in or immediately adjacent to the selectivity filter. Residues boxed in green participate in intersubunit interactions between helices A′B′ and C′D′. Residues boxed in orange are engaged in interactions between helices A′B′ of one subunit and S4/S4-S5 linker/S5 of an adjacent subunit. Positions of single-amino acid missense mutations that cause retinitis pigmentosa are highlighted in red in hCNGA1 and orange in hCNGB1, and those cause achromatopsia are highlighted in cyan in hCNGA3 and green in hCNGB3. The disease-causing mutations are listed and color-coded on both sides of the sequences. TAX-2 does not form functional homomeric channels but associates with TAX-4 to form functional heteromeric channels, both in heterologous expression systems and native cells. b, c, Mapping the disease-causing mutations listed in a on the TAX-4 protomer structure, shown in the same orientation here as in Fig. 1c.