The epsin N-terminal homology (ENTH) ___domain is a structural ___domain that is found in proteins involved in endocytosis and cytoskeletal machinery.
 ENTH ___domain of epsin-1.[1] | |||||||||
| Identifiers | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Symbol | ENTH | ||||||||
| Pfam | PF01417 | ||||||||
| InterPro | IPR001026 | ||||||||
| PROSITE | PDOC50942 | ||||||||
| SCOP2 | 1edu / SCOPe / SUPFAM | ||||||||
| OPM superfamily | 38 | ||||||||
| OPM protein | 1h0a | ||||||||
| CDD | cd03571 | ||||||||
| |||||||||
Structure
editThis ___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.[2] An N-terminal helix folds back, forming a deep basic groove that forms the binding pocket for the Ins(1,4,5)P3 ligand.[1] The lipid ligand is coordinated by residues from surrounding alpha-helices and all three phosphates are multiply coordinated.
Interactions with the lipid bilayer
editProteins 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.[3] 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, 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.
Human proteins containing this ___domain
editReferences
edit- ^ a b Ford MG, Mills IG, Peter BJ, et al. (September 2002). "Curvature of clathrin-coated pits driven by epsin". Nature. 419 (6905): 361–6. doi:10.1038/nature01020. PMID 12353027. S2CID 4372368.
- ^ Chen H, Bateman A, de Camilli P, Hyman J, Panepucci E, Brunger AT (2002). "The ENTH ___domain". FEBS Lett. 513 (1): 11–18. doi:10.1016/S0014-5793(01)03306-3. PMID 11911874. S2CID 25544319.
- ^ Kay BK, Yamabhai M, Wendland B, Emr SD (1999). "Identification of a novel ___domain shared by putative components of the endocytic and cytoskeletal machinery". Protein Sci. 8 (2): 435–8. doi:10.1110/ps.8.2.435. PMC 2144257. PMID 10048338.