multimerization

Multimerization refers to the process by which multiple individual subunits (monomers) assemble into a larger, discrete complex called a multimer. Multimers range from dimers (two subunits) to higher-order oligomers and sometimes polymers. The subunits may be identical (homo-multimers) or different (heteromultimers).

Multimerization is driven mainly by noncovalent interactions such as hydrophobic contacts, hydrogen bonds, and electrostatic interactions, although covalent bonds such as disulfide linkages can stabilize or lock assemblies. Interfaces between subunits require complementary shapes and surfaces. The assembly can be regulated by ligand binding, post-translational modifications, pH, and ionic strength. Some systems use chaperones or scaffolds to promote or control assembly.

Biological roles: Many proteins function as multimers, and the assembly can influence activity, stability, and regulation. Hemoglobin, for example, is a tetramer whose quaternary structure enables cooperative oxygen binding. Transcription factors may require dimerization for DNA binding. Receptor proteins, particularly receptor tyrosine kinases, often dimerize or oligomerize upon ligand binding to propagate signals. Immunoglobulins are built from multiple polypeptide chains linked by disulfide bonds. Multimerization also plays a central role in the assembly of viral capsids and in the formation of cytoskeletal polymers such as actin and tubulin.

Methods and implications: Multimerization can be studied by structural and biophysical methods, including cryo-electron microscopy, X-ray crystallography, size-exclusion chromatography, analytical ultracentrifugation, crosslinking, and mass spectrometry. Aberrant multimerization or improper assembly can contribute to disease, while controlled multimerization is exploited in biotechnology to modulate function or create programmable materials.

Terminology: The term oligomer describes assemblies of several subunits; dimers, trimers, and tetramers are common forms. The process is often dynamic, with subunits associating and dissociating to shift between functional states.