Monotopic

Monotopic is a term used in cell biology to describe a class of membrane-associated proteins that are anchored to one leaflet of a lipid bilayer and do not span the membrane. In monotopic proteins, the hydrophobic region that anchors the protein either associates with a single leaflet as a helix or forms a surface-embedded lipid anchor, while the protein remains on one side of the membrane. This distinguishes monotopic proteins from bitopic and polytopic proteins, which cross the bilayer with one or more transmembrane segments, respectively, and from peripheral proteins that do not insert into the bilayer.

Anchoring can occur by covalent lipid modifications, such as palmitoylation or GPI anchoring, or by a hydrophobic region that inserts into the outer leaflet without crossing the hydrophobic core. The topology can be static or dynamic, with the active sites oriented toward either the cytosol or the extracellular/periplasmic space, depending on the protein and membrane system.

Functional roles of monotopic proteins include enzymes that catalyze reactions at the membrane interface, signaling proteins that recruit or activate other factors at one membrane surface, and regulators that modulate lipid composition or membrane curvature. They are often involved in processes at specific membranes, such as the plasma membrane or endomembrane systems, and can respond to lipid composition and localization cues.

Determining monotopic topology can be challenging: computational prediction tools for transmembrane helices may misclassify monotopic segments as spans, and experimental approaches such as protease protection assays, lipidation studies, and structural analysis are used to establish topology.

In summary, monotopic proteins are membrane-associated factors that do not traverse the bilayer, instead interacting with and anchoring to a single leaflet to perform their cellular functions.