(A) Side view of atomic structure of a C. elegans homomeric, homotypic INX-6 gap junction full channel, determined by Oshima et al., 2016 (PDB I.D. 5H1R, rcsb.org; Berman et al., 2000), viewed at aquaria.ws (O'Donoghue et al., 2015). Vertical gray bars indicate approximate location of the plasma membranes of apposed cells; ‘Ext’ indicates the extracellular region where octameric hemichannels associate via extracellular loops to form an enclosed channel in the region classically identified by TEM as the ‘gap’ between closely aligned plasma membranes. Beta-strands (yellow) in the extracellular loops contribute to walling off the pore. Single innexin subunit is highlighted in the representation on the right. (B,C) Model for INX-8 hemichannel based on homology alignment (25% identity) to INX-6 (PDB 5H1Q) as viewed from the cytoplasm (B) or extracellular region (C). Single subunits highlighted in representations on right. In wild-type, this hemichannel is comprised of both INX-8 and INX-9 subunits (84% identity), and associates with germline hemichannels comprised of INX-14+INX-21 or INX-14+INX-22. (D) Position of INX-8 D24N, suppressor mutation of T239I. NT indicates approximate region of N-terminus. A kinked region (black arrow) allows the cytoplasmic structure of the subunits (cytoplasmic loops and C-termini) to form a dome at the pore entry. Amino termini line the pore as a funnel; a loop in the amino terminus allows for an interaction with residues in the dome (Oshima et al., 2016). D24 (red) lies near the D21 residue predicted by homology with INX-6 (D25) to interact with the cytoplasmic dome. (E) View of INX-8 subunit from extracellular face. Aqua arrow indicates approximate angle of channel, which lies in a plane above the highlighted subunit. (F) INX-8 T239 is predicted to lie adjacent to beta-strands (yellow) contributing to extracellular loop formation integral to hemichannel-hemichannel association. Disulfide bonds forming between cysteines that are invariant in the innexin family are indicated by dotted lines (one marked with arrow). E1H, helix formed in the first extracellular loop that contributes to constriction of the pore in the extracellular region. E2H, helix formed in the second extracellular loop that lies external to the channel. E1 and E2 are loops formed in the respective extracellular regions. Oshima et al., 2016 for details.