homotrimer

A homotrimer is a protein complex formed by three identical subunits that assemble to create a single functional unit. The association is typically mediated by non-covalent interactions, though covalent cross-links such as disulfide bonds can occur in some cases. Each subunit shares the same amino acid sequence and fold, and the complex commonly displays threefold (C3) rotational symmetry around a central axis.

In many proteins, trimerization influences stability, catalysis, binding, or signaling. The threefold arrangement can bring together catalytic residues from all subunits, generate a composite binding interface, or enable cooperative regulation of activity. In signaling, trimeric ligands or receptors can engage multiple copies of a partner protein simultaneously. Tumor necrosis factor alpha (TNF-α) is a classic example of a homotrimeric cytokine that binds three receptors.

Homotrimers are found in diverse biological contexts, including cytokines, viral capsid proteins, and certain enzymes. The quaternary structure can evolve through gene duplication and diversification of three identical subunits, with interfaces tuned for specific affinity and specificity.

Characterization relies on structural and biochemical methods. X-ray crystallography and cryo-electron microscopy reveal threefold symmetry and contact interfaces; analytical ultracentrifugation, size-exclusion chromatography, and native electrophoresis estimate oligomeric state; cross-linking experiments provide additional constraints. Understanding homotrimers aids in interpreting mechanism, regulation, and potential therapeutic targeting where trimeric assembly is functionally essential.