heteropentamers

Heteropentamers are protein complexes composed of five subunits where more than one type of subunit is present. This distinguishes them from homopentamers, which contain five copies of a single subunit type. The term is commonly used for a class of multi-subunit assemblies in which the arrangement and identity of subunits influence the complex’s properties.

A prominent context for heteropentamers is in pentameric ligand-gated ion channels, which form pentameric pore structures that open in response to ligand binding. Examples include nicotinic acetylcholine receptors (nAChRs), GABA type A receptors, glycine receptors, and some serotonin receptors (5-HT3). In these receptor families, different subunits combine to yield diverse receptor subtypes with distinct tissue distribution, ligand sensitivities, and gating kinetics. The subunits contribute to the architecture around the central pore, including the interfaces that create binding sites for neurotransmitters and allosteric modulators.

Subunit composition is typically encoded by multiple gene families, and assembly occurs in the endoplasmic reticulum with specific stoichiometries that can vary by subtype and species. The precise combination of subunits determines pharmacological properties, such as sensitivity to agonists, antagonists, and allosteric drugs, as well as channel conductance and kinetics. Heteropentameric assemblies thereby enable functional diversity and tissue-specific signaling, while also presenting multiple targets for therapeutic intervention.

Dysfunction or altered expression of heteropentameric receptors has been implicated in a range of neurological and neuromuscular disorders, and these receptors are common targets in pharmacology for anesthetics, sedatives, anticonvulsants, and other drugs.