FIGURE 7-17 Charged residues can orchestrate the assembly of multimeric membrane proteins. The T cell receptor (TCR) for antigen is composed of four separate dimers: an αβ pair directly responsible for antigen recognition, and accessory subunits collectively referred to as the CD3 complex. These accessory subunits include the γ, δ, ε, and ζ subunits. The ζ subunits form a disulfide-linked homodimer. The γ and δ subunits occur in complex with an ε subunit, to generate a γε and a δε pair. The transmembrane segments of the TCR α and β chains each contain positively charged residues (blue). These residues allow recruitment of corresponding δε and γε heterodimers, which carry negative charges (red) at the appropriate depth in the hydrophobic core of the bilayer. The ζ homodimer docks onto the charges in the TCR α chain (dark green), while the γε and δε subunit pairs find their corresponding partners deeper down in the hydrophobic core on both the TCR α and TCR β chain (light green). Charged residues in otherwise nonpolar transmembrane segments can thus guide assembly of higher-order structures.

[Data from K. W. Wucherpfennig et al., 2010, Cold Spring Harb. Perspect. Biol., 2:a005140, PDB ID 1xmw; M. E. Call et al., 2006, Cell, 127:355, PDB ID 2hac; and L. Kjer-Nielsen et al., 2003, Immunity, 18:53, PDB ID 1mi5.]