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Science 13 November 1998: Vol. 282. no. 5392, pp. 1327 - 1332 DOI: 10.1126/science.282.5392.1327
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Reports
A Structural Explanation for the Recognition of Tyrosine-Based Endocytotic Signals
David J. Owen,
Philip R. Evans
*
Many cell surface proteins are marked for endocytosis by a
cytoplasmic sequence motif, tyrosine-X-X-(hydrophobic residue), that is
recognized by the µ2 subunit of AP2 adaptors. Crystal structures of
the internalization signal binding domain of µ2 complexed with the
internalization signal peptides of epidermal growth factor receptor and
the trans-Golgi network protein TGN38 have been determined at 2.7 angstrom resolution. The signal peptides adopted an extended
conformation rather than the expected tight turn. Specificity was
conferred by hydrophobic pockets that bind the tyrosine and leucine in
the peptide. In the crystal, the protein forms dimers that could
increase the strength and specificity of binding to dimeric receptors.
Medical Research Council Laboratory of Molecular Biology, Hills
Road, Cambridge CB2 2QH, UK.
*
To whom correspondence should be addressed. E-mail:
pre{at}mrc-lmb.cam.ac.uk
Read the Full Text
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162, 909-918
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277, 35378-35385
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- Phosphorylation of the AP2 {micro} subunit by AAK1 mediates high affinity binding to membrane protein sorting signals.
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J. Cell Biol.
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- Cutting Edge: Internalization of Transduced E-Selectin by Cultured Human Endothelial Cells: Comparison of Dermal Microvascular and Umbilical Vein Cells and Identification of a Phosphoserine-Type Di-leucine Motif.
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J. Immunol.
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- {micro}2 Binding Directs the Cystic Fibrosis Transmembrane Conductance Regulator to the Clathrin-mediated Endocytic Pathway.
- K. M. Weixel and N. A. Bradbury (2001)
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- Immature Human Dendritic Cells Express Asialoglycoprotein Receptor Isoforms for Efficient Receptor-Mediated Endocytosis.
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- Golgi-localized, gamma-Ear-containing, ADP-Ribosylation Factor-binding Proteins: Roles of the Different Domains and Comparison with AP-1 and Clathrin.
- J. Hirst, M. R. Lindsay, and M. S. Robinson (2001)
Mol. Biol. Cell
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- Adaptins. The Final Recount.
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Mol. Biol. Cell
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- Trafficking and cell surface stability of ENaC.
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Am J Physiol Renal Physiol
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- Yeast Gga Coat Proteins Function with Clathrin in Golgi to Endosome Transport.
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Mol. Biol. Cell
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- Stonin 2: An Adaptor-like Protein That Interacts with Components of the Endocytic Machinery.
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- Distribution and Function of Ap-1 Clathrin Adaptor Complexes in Polarized Epithelial Cells.
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152, 595-606
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- Tyrosine Decaging Leads to Substantial Membrane Trafficking during Modulation of an Inward Rectifier Potassium Channel.
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- Negative Factor from SIV Binds to the Catalytic Subunit of the V-ATPase to Internalize CD4 and to Increase Viral Infectivity.
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Mol. Biol. Cell
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- Vps10p Transport from the trans-Golgi Network to the Endosome Is Mediated by Clathrin-coated Vesicles.
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- PTH-Induced Downregulation of the Type IIa Na/Pi-Cotransporter Is Independent of Known Endocytic Motifs.
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- Distinct Trafficking Pathways Mediate Nef-Induced and Clathrin-Dependent Major Histocompatibility Complex Class I Down-Regulation.
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- Mutation of a Conserved Residue (D123) Required for Oligomerization of Human Immunodeficiency Virus Type 1 Nef Protein Abolishes Interaction with Human Thioesterase and Results in Impairment of Nef Biological Functions.
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- Identification of a Novel Member of the Chloride Intracellular Channel Gene Family (CLIC5) That Associates with the Actin Cytoskeleton of Placental Microvilli.
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Mol. Biol. Cell
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- Bi-directional trafficking between the trans-Golgi network and the endosomal/lysosomal system.
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- The Inhibitory Function of CTLA-4 Does Not Require Its Tyrosine Phosphorylation.
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- Efficient Export of the Vesicular Stomatitis Virus G Protein from the Endoplasmic Reticulum Requires a Signal in the Cytoplasmic Tail That Includes Both Tyrosine-based and Di-acidic Motifs.
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Mol. Biol. Cell
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- Crystal structure of the alpha appendage of AP-2 reveals a recruitment platform for clathrin-coat assembly.
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PNAS
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