Role of the ENTH domain in phosphatidylinositol-4,5-bisphosphate binding and endocytosis

被引：383

作者：

Itoh, T

Koshiba, S

Kigawa, T

Kikuchi, A

Yokoyama, S

Takenawa, T

机构：

[1] Univ Tokyo, Inst Med Sci, Dept Biochem, Minato Ku, Tokyo 1088639, Japan

[2] RIKEN, Genom Sci Ctr, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan

[3] RIKEN, Harima Inst SPring 8, Cellular Signaling Lab, Sayo, Hyogo 6795148, Japan

[4] Hiroshima Univ, Sch Med, Dept Biochem, Minami Ku, Hiroshima 7348551, Japan

[5] Univ Tokyo, Grad Sch Sci, Dept Biophys & Biochem, Bunkyo Ku, Tokyo 1130033, Japan

来源：

SCIENCE | 2001年 / 291卷 / 5506期

关键词：

D O I：

10.1126/science.291.5506.1047

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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)P-2]. 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 Lys(76) --> Ala(76), 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)P-2 is essential for endocytosis mediated by clathrin-coated pits.

引用

页码：1047 / 1051

页数：5

共 28 条

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