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Science (American Association for the Advancement of Science), 2001-02, Vol.291 (5506), p.1047-1051
2001
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Autor(en) / Beteiligte
Titel
Role of the ENTH Domain in Phosphatidylinositol-4,5-Bisphosphate Binding and Endocytosis
Ist Teil von
  • Science (American Association for the Advancement of Science), 2001-02, Vol.291 (5506), p.1047-1051
Ort / Verlag
Washington, DC: American Society for the Advancement of Science
Erscheinungsjahr
2001
Quelle
American Association for the Advancement of Science
Beschreibungen/Notizen
  • 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 [Ptdlns(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. Over-expression 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 Ptdlns(4,5)P2is essential for endocytosis mediated by clathrin-coated pits.

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