The epsin N-terminal homology (ENTH) domain is a structural domain that is found in proteins involved in

endocytosis Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested material. E ...

and

cytoskeletal The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compo ...

machinery.

Structure

This domain is approximately 150 amino acids in length and is always found located at the N-termini of proteins. The domain forms a compact globular structure, composed of nine alpha-helices connected by loops of varying length. The general topology is determined by three helical hairpins that are stacked consecutively with a right hand twist. An N-terminal helix folds back, forming a deep basic groove that forms the binding pocket for the Ins(1,4,5)P3 ligand. The lipid ligand is coordinated by residues from surrounding alpha-helices and all three phosphates are multiply coordinated.

Interactions with the lipid bilayer

Proteins containing this domain have been found to bind PtdIns(4,5)P2 and Ins(1,4,5)P3 suggesting that the domain is a membrane-interacting module. The main function of proteins containing this domain appears to be to act as accessory clathrin adaptors in endocytosis, epsin is able to recruit and promote clathrin polymerisation on a lipid monolayer, but may have additional roles in signalling and actin regulation. Epsin causes a strong degree of membrane curvature and tubulation, even fragmentation of membranes with a high PtdIns(4,5)P2 content. Epsin binding to membranes facilitates their deformation by insertion of the N-terminal helix into the inner leaflet of the bilayer, pushing the head groups apart. This would reduce the energy needed to curve the membrane into a vesicle, making it easier for the clathrin cage to fix and stabilise the curved membrane. This points to a pioneering role for epsin in vesicle budding, as it provides both a driving force and a link between membrane invagination and clathrin polymerisation. In particular, epsin-1 shows specificity for the membrane glycophospholipid

phosphatidylinositol-4,5-bisphosphate Phosphatidylinositol 4,5-bisphosphate or PtdIns(4,5)''P''2, also known simply as PIP2 or PI(4,5)P2, is a minor phospholipid component of cell membranes. PtdIns(4,5)''P''2 is enriched at the plasma membrane where it is a substrate for a number of ...

, however not all ENTH domains bind to this molecule. Binding causes tubulation of liposomes and ''in vivo'' this membrane-binding function is normally coordinated with clathrin polymerisation. The N-terminal alpha-helix of this domain is hydrophobic and inserts into the membrane like a wedge and helps to drive membrane curvature.

Structure

Interactions with the lipid bilayer

Human proteins containing this domain

References

External links

Further reading