Significance Receptors that separate ligand recognition and intracellular signaling into separate protein subunits are ubiquitous in immunity. These subunits mix and match to create combinatorial functional diversity. The transmembrane domains of these receptors assemble through the interaction between two acidic and one basic residue on different helices. Using computational methods to study the DAP12-NKG2C receptor complex, we identified a polar motif in which a singly-protonated Asp-Asp pair forms a carboxyl-carboxylate clamp that clasps a charged Lys side chain in the membrane. This local interaction allows dynamic variations in other regions of the helices that tolerate sequence diversity of the interacting subunits in this class of receptors, which signal through multisubunit clustering rather than propagation of rigid conformational changes through the membrane.