Publication Date:
2001-02-13
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Itoh, T -- Koshiba, S -- Kigawa, T -- Kikuchi, A -- Yokoyama, S -- Takenawa, T -- New York, N.Y. -- Science. 2001 Feb 9;291(5506):1047-51.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11161217" target="_blank"〉PubMed〈/a〉
Keywords:
Adaptor Proteins, Vesicular Transport
;
Amino Acid Motifs
;
Amino Acid Substitution
;
Animals
;
COS Cells
;
Carrier Proteins/*chemistry/*metabolism
;
Cercopithecus aethiops
;
Clathrin/metabolism
;
Coated Pits, Cell-Membrane/metabolism
;
DNA-Binding Proteins/metabolism
;
*Endocytosis
;
Epidermal Growth Factor/metabolism
;
Inositol Phosphates/metabolism
;
Liposomes/metabolism
;
Models, Molecular
;
Neuropeptides/*chemistry/*metabolism
;
Nuclear Magnetic Resonance, Biomolecular
;
Phosphatidylinositol 4,5-Diphosphate/*metabolism
;
Protein Conformation
;
Protein Structure, Secondary
;
Protein Structure, Tertiary
;
Recombinant Fusion Proteins/chemistry/metabolism
;
Transcription Factors/metabolism
;
*Vesicular Transport Proteins
;
Zinc Fingers
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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