heterotrimeric

Heterotrimeric describes a protein complex composed of three subunits that are different from one another. In contrast to homotrimeric assemblies, where all three subunits are identical, heterotrimers rely on distinct polypeptides to provide diverse regulatory, catalytic, or binding properties. The term is widely used in molecular biology to describe multisubunit assemblies that assemble in defined stoichiometries from separate genes.

The best-known example is the heterotrimeric G protein family, consisting of Gα, Gβ, and Gγ subunits. In the inactive state, Gα binds GDP and associates with the Gβγ dimer. Upon receptor activation, GDP is exchanged for GTP on Gα, prompting dissociation of Gα-GTP from Gβγ. The two resulting entities regulate a range of effectors, including enzymes and ion channels, at the plasma membrane and thereby propagate signals to intracellular pathways. Subunit composition and post-translational modifications influence signaling specificity, duration, and subcellular localization.

Heterotrimeric assemblies also occur in other biological contexts. Some collagens form heterotrimeric triple helices with two different alpha chains, as in type I collagen (two α1 chains and one α2 chain). In addition, certain transcription factors are heterotrimeric, comprising three distinct subunits that cooperatively bind DNA and regulate transcription, such as NF-Y. Across systems, heterotrimers arise from separate genes and assemble in regulated ways, often with chaperone assistance and spatial constraints.

Disruptions to subunit expression, assembly, or interactions can alter function, contributing to disease and offering targets for therapeutic intervention.