Figure 4.

Cl⁻ triggers a molecular switch enabling NC1‐directed oligomerization. In the absence of Cl⁻, Arg76 forms intramolecular salt‐bridge with Asp78 and/or Glu40 (A). Extracellular Cl⁻ disrupts Arg76‐Asp78 salt bridge by electrostatic screening (B). Cl⁻ binds each monomer by coordination with the Arg76 backbone amide, thus orienting the side toward an opposing NC1 timer (C). Reorientation of the Arg76 side chain allows for two protomers to bind one another through a Arg76‐Glu175:Asn187 salt‐bridge (D). Each bound Cl⁻ ion can also coordinate Arg179 of the opposing protomer for a total up to 12 Cl⁻ mediated interactions per hexamer (E).