The cytoplasmic domain of the T-cell receptor zeta subunit does not form disordered dimers.

Intrinsically disordered regions in proteins play active roles in recognition, signaling and molecular sorting. They often undergo coupled folding and binding giving rise to largely ordered interfaces with their binding partners. The cytoplasmic region of the T-cell receptor zeta subunit (ζcyt) has been previously proposed to specifically dimerize in the absence of a disorder-to-order transition, suggesting an intriguing dimerization mechanism that may involve multiple transient interfaces. We show here using analytical ultracentrifugation, NMR, size-exclusion chromatography (SEC) and multi-angle light scattering that neither ζcyt nor the cytoplasmic region of CD3ε significantly populates a dimeric state but that they are mostly monomers in solution up to millimolar concentrations. They experience a salt- and concentration-dependent shift of their elution volume in SEC previously interpreted as dimerization. Our data show that ζcyt does not form a highly disordered protein complex and leaves open the question as to whether completely disordered dimers (or other oligomers) exist in nature.