tetramerization

Tetramerization is the association of four molecular subunits to form a tetramer, a type of quaternary structure. Subunits may be identical (homotetramer) or different (heterotetramer). Tetramerization can affect stability, allosteric regulation, cooperative binding, and catalytic properties. It is common in enzymes, structural proteins, and transcription factors.

Hemoglobin is the archetypal tetramer, consisting of two alpha and two beta subunits, whose tetrameric assembly underlies cooperative oxygen binding. Lactate dehydrogenase forms a homotetramer, contributing to catalytic efficiency. The tumor suppressor protein p53 functions as a tetramer; disruption of tetramerization impairs DNA binding and function.

Interfaces between subunits are formed by hydrophobic interactions, hydrogen bonds, and salt bridges; motifs such as coiled-coil domains can promote tetramerization. Assembly can be driven by ligand binding, pH, ionic strength, or post-translational modifications, and chaperones can facilitate proper subunit association.

Studying tetramerization employs structural and biophysical methods including X-ray crystallography, cryo-electron microscopy, nuclear magnetic resonance, analytical ultracentrifugation, and size-exclusion chromatography to reveal subunit arrangement and assembly dynamics.

Relevance and applications include protein engineering, regulation of signaling pathways, and drug design. Aberrant tetramerization or dysregulated tetramer interfaces can compromise function and have been explored as therapeutic targets, making an understanding of tetramerization important across biochemistry and medicine.