Heterohexamer

A heterohexamer is a protein complex composed of six subunits, with at least two distinct subunit types. The term contrasts with homohexamer, where all six subunits are identical.

Heterohexamers often form ring-shaped assemblies, with subunits arranged around a central pore. The subunits may be paralogs or different polypeptides, contributing diverse functional sites and regulatory features. The stoichiometry is fixed to six, but subunit composition can vary between organisms or conditions.

Notable examples include the eukaryotic MCM2-7 helicase complex, a heterohexamer composed of six related but non-identical subunits (MCM2, MCM3, MCM4, MCM5, MCM6, MCM7) that encircles DNA to unwind it during replication.

Another example is the base of the 19S regulatory particle of the proteasome in eukaryotes, a heterohexamer formed by six distinct AAA+ ATPase subunits (Rpt1–Rpt6) that drive substrate unfolding and translocation.

Functional advantages of heterohexameric organization include specialization of subunits for different tasks, coordinated allosteric regulation, and potential asymmetric activity across the ring. Evolutionarily, subunit diversification through gene duplication can yield heterohexameric complexes with new regulatory capabilities.

Techniques for studying heterohexamers include cryo-electron microscopy, X-ray crystallography, cross-linking mass spectrometry, and native mass spectrometry; these reveal subunit arrangement and interfaces.