Significance Many activating immunoreceptors associate, via interactions between transmembrane domains, with adaptor molecules that mediate signaling for leukocyte activation. To date, the best characterized form of receptor complex assembly depends on a single basic transmembrane (TM) domain residue. We now describe a second, completely different solution for TM-mediated receptor assembly, found in three different Fc receptor TM domains, and involving a more complex polar/aromatic interface. Residues in the core of this interaction motif can also regulate receptor protein turnover. Thus, multiple solutions for TM-mediated receptor assembly with signaling modules have evolved. These findings may provide more broadly useful insights into how other immune receptors that do not contain charged residues in their TM domains assemble into complexes with signaling adaptor molecules.