heterotrimers

A heterotrimer is a protein complex composed of three non-identical polypeptide subunits assembled to form a functional unit. Each subunit is typically encoded by a separate gene and contributes a distinct structural or functional element to the overall activity of the complex.

Assembly and organization: The three subunits assemble through specific interfaces to produce a defined stoichiometry, usually 1:1:1. Assembly can occur during translation or afterward in the cytosol or extracellular matrix, often aided by chaperone proteins and proper post-translational modifications that promote correct folding and stability.

Examples and roles: Heterotrimeric G proteins, composed of Gα, Gβ, and Gγ, relay signals from activated receptors; Gα binds and hydrolyzes GTP, while Gβ and Gγ mediate coupling to downstream effectors. Collagen type I is a heterotrimer of two α1(I) chains and one α2(I) chain, providing the fibrous structural framework of connective tissue. The NF-Y transcription factor is a heterotrimer of NF-YA, NF-YB, and NF-YC that binds CCAAT motifs to regulate gene expression. Other heterotrimers occur in various signaling, enzymatic, and structural contexts, illustrating the diversity of functional themes that arise from three distinct subunits.

Function and regulation: The subunits cooperate to produce activity; the presence and interaction of all three are often required for function. Subunit composition can influence binding surfaces, catalytic centers, and regulatory responses, allowing combinatorial diversity and tight control across cellular pathways. Disruptions in any subunit can alter or abolish activity, with potential physiological consequences.

Significance: Heterotrimers are studied across biochemistry and cell biology to understand how multi-subunit coordination governs signaling, gene regulation, and tissue architecture. Structural and biophysical methods, along with genetic approaches, elucidate their assembly and mechanisms.