Heterodimeric

Heterodimeric describes a protein complex composed of two different polypeptide subunits held together by non-covalent interactions. In contrast to homodimers, where two identical subunits form the dimer, heterodimers exhibit distinct subunit compositions that can endow unique functional properties. Heterodimerization is common in many protein families, including transcription factors, receptors, and enzymes.

Examples include the transcription factor NF-κB, which functions as a p50/p65 heterodimer, and the AP-1 transcription factor formed by Fos and Jun family members. In receptors, GABA-B receptors are heterodimers of GABAB1 and GABAB2 subunits; many receptor tyrosine kinases and ion channels also assemble as heterodimers to create ligand-binding and signaling diversity.

Functional significance: increases diversity of binding motifs, regulatory capabilities, and tissue specificity. The subunits can influence DNA binding, subcellular localization, stability, and interaction with cofactors. Subunit swap or differential expression can modulate signaling outcomes, and dysregulation can contribute to disease.

Detection and study: co-immunoprecipitation, pull-down assays, yeast two-hybrid, cross-linking, and mass spectrometry are used to demonstrate subunit association. Structural methods like X-ray crystallography and cryo-electron microscopy reveal interaction interfaces, while genetic approaches to alter subunit expression help clarify each subunit’s roles.