Role of the ENTH domain in phosphatidylinositol-4, 5-bisphosphate binding and endocytosis
T Itoh, S Koshiba, T Kigawa, A Kikuchi, S Yokoyama… - Science, 2001 - science.org
T Itoh, S Koshiba, T Kigawa, A Kikuchi, S Yokoyama, T Takenawa
Science, 2001•science.orgEndocytic proteins such as epsin, AP180, and Hip1R (Sla2p) share a conserved modular
region termed the epsin NH2-terminal homology (ENTH) domain, which plays a crucial role
in clathrin-mediated endocytosis through an unknown target. Here, we demonstrate a strong
affinity of the ENTH domain for phosphatidylinositol-4, 5-bisphosphate [PtdIns (4, 5) P2].
With nuclear magnetic resonance analysis of the epsin ENTH domain, we determined that a
cleft formed with positively charged residues contributed to phosphoinositide binding …
region termed the epsin NH2-terminal homology (ENTH) domain, which plays a crucial role
in clathrin-mediated endocytosis through an unknown target. Here, we demonstrate a strong
affinity of the ENTH domain for phosphatidylinositol-4, 5-bisphosphate [PtdIns (4, 5) P2].
With nuclear magnetic resonance analysis of the epsin ENTH domain, we determined that a
cleft formed with positively charged residues contributed to phosphoinositide binding …
Endocytic proteins such as epsin, AP180, and Hip1R (Sla2p) share a conserved modular region termed the epsin NH2-terminal homology (ENTH) domain, which plays a crucial role in clathrin-mediated endocytosis through an unknown target. Here, we demonstrate a strong affinity of the ENTH domain for phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P2]. With nuclear magnetic resonance analysis of the epsin ENTH domain, we determined that a cleft formed with positively charged residues contributed to phosphoinositide binding. Overexpression of a mutant, epsin Lys76 → Ala76, with an ENTH domain defective in phosphoinositide binding, blocked epidermal growth factor internalization in COS-7 cells. Thus, interaction between the ENTH domain and PtdIns(4,5)P2 is essential for endocytosis mediated by clathrin-coated pits.
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