ENTHEpsin N-terminal homology (ENTH) domain
|SMART accession number:||SM00273|
|Interpro abstract (IPR013809):|
The ENTH (Epsin N-terminal homology) 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 9 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 [(PUBMED:11911874)]. An N-terminal helix folds back, forming a deep basic groove that forms the binding pocket for the Ins(1,4,5)P3 ligand [(PUBMED:12353027)]. The ligand is coordinated by residues from surrounding alpha-helices and all three phosphates are multiply coordinated. The coordination of Ins(1,4,5)P3 suggests that ENTH is specific for particular head groups.
Proteins containing this domain have been found to bind PtdIns(4,5)P2 and PtdIns(1,4,5)P3 suggesting that the domain may be 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 [(PUBMED:10048338)]. 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 outer 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.
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- Evolution (species in which this domain is found)
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