Structural alignment used for modeling of MEC-4 and UNC-8.

<p>MEC-4_A, MEC-4_B, MEC-4_C, MEC-4_H and UNC-8_A, UNC-8_B, UNC-8_C, UNC-8_H were treated independently from one another. Each subunit is modeled to the superimposed subunits of 2QTS or 3HGC, respectively. Secondary structural elements are color-coded (red: helices, blue: β-strands). Asterisks below the sequences denote identical, and dots similar residues. Amino acid substitutions corresponding to mutant alleles are depicted in bold and are underlined, for specifics see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0012814#pone-0012814-t001" target="_blank">Table 1</a>. Solid lines above the alignment denote parts of the modeled hand (turquoise: forearm, light blue: fingers, yellow: thumb).</p

Stereo views of the environment of the dominant, gain-of-function <i>mec-4</i> allele <i>u231</i> (here A408V).

<p>The sidechain of A408 was substituted by Val and is shown in red. I and II denote transmembrane helices I and II. <b>a</b>: Yellow, blue and green denote the different subunits of <i>mec-4</i> modeled to the three different subunits of the crystal structure 2QTS. <b>b</b>: Yellow, blue and green denote the crystallographic equivalent subunits of the trimer derived by application of crystallographic symmetry. The subunit was modeled to the subunit of 3HGC. The same helical segments are shown as in Figure 3a.</p

The environment (within 9 Å) of the semi-dominant gain-of-function <i>unc-8</i> allele <i>e49</i>, here A266T, in the 4 superimposed models of a subunit of UNC-8.

<p>For clarity, only ribbons are drawn. Yellow, blue, green and orange denote the different modeled subunits of <i>unc-8</i>. The sidechain of A266 was substituted in the picture by T266 and is shown in red.</p

Superposition of the four subunits of MEC-4 modeled on the 3 subunits of the crystal structure of the closed acid sensing ion channel of chicken (PDB ID: 2QTS) and on the minimal function channel (PDB ID: 3HGC).

<p>Colors denote the model confidence factor of the SWISS-MODEL server; dark blue regions denote high confidence, green to red gradually lower reliability. Lower reliability is assigned if the template residues (in A, B and C of 2QTS and 3HGC) differ from one another or to sparse loops incorporated from other structures. The arrow marks the position of <i>e49</i> in the modeled UNC-8 subunits (not shown). NC1 and NC2 denote the position of two blocks of sequence in MEC-4 which have no counterpart in the alignment and therefore are not modeled.</p

Ion channel mutants.

<p>The molecular characteristics, the associated mutant phenotypes and the localization of amino-acid substitutions on the model are indicated. TM: Transmembrane.</p