homooligomerization

Homooligomerization is the assembly of multiple identical protein subunits into a larger, functional complex called an oligomer. When all subunits are the same, the complex is a homooligomer (for example, dimers, trimers, tetramers, hexamers). This is distinguished from heterooligomerization, in which subunits differ in sequence and function.

Assembly is driven by interactions at subunit interfaces, including coiled-coil domains, hydrophobic patches, hydrogen bonding, and sometimes covalent disulfide bonds. Subunit interfaces can impose symmetry and enable cooperative behavior. Oligomerization can be constitutive or regulated by factors such as ligand binding, phosphorylation, pH, redox state, and proteolysis.

Functional roles include increased stability, allosteric regulation, creation of new catalytic or binding properties, and structural scaffolding. Homooligomers enable cooperative substrate binding, formation of channels or cages, and the assembly of multi-subunit enzymes. Examples of homooligomeric assemblies include p53 tetramers, ferritin iron-storage cages, tropomyosin dimers, and Hsp90 dimers.

Studying homooligomerization uses techniques such as size-exclusion chromatography with light scattering, analytical ultracentrifugation, cross-linking mass spectrometry, X-ray crystallography, and cryo-electron microscopy.

Abnormal homooligomerization can contribute to disease when it alters signaling, stability, or aggregation propensity, including cancer-related misregulation and neurodegenerative amyloid formation.