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Science 13 November 1998:
Vol. 282. no. 5392, pp. 1327 - 1332
DOI: 10.1126/science.282.5392.1327

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


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Trafficking and cell surface stability of ENaC.
D. Rotin, V. Kanelis, and L. Schild (2001)
Am J Physiol Renal Physiol 281, F391-F399
   Abstract »    Full Text »    PDF »
Yeast Gga Coat Proteins Function with Clathrin in Golgi to Endosome Transport.
G. Costaguta, C. J. Stefan, E. S. Bensen, S. D. Emr, and G. S. Payne (2001)
Mol. Biol. Cell 12, 1885-1896
   Abstract »    Full Text »    PDF »
Stonin 2: An Adaptor-like Protein That Interacts with Components of the Endocytic Machinery.
J. A. Martina, C. J. Bonangelino, R. C. Aguilar, and J. S. Bonifacino (2001)
J. Cell Biol. 153, 1111-1120
   Abstract »    Full Text »    PDF »
Distribution and Function of Ap-1 Clathrin Adaptor Complexes in Polarized Epithelial Cells.
H. Folsch, M. Pypaert, P. Schu, and I. Mellman (2001)
J. Cell Biol. 152, 595-606
   Abstract »    Full Text »    PDF »
Tyrosine Decaging Leads to Substantial Membrane Trafficking during Modulation of an Inward Rectifier Potassium Channel.
Y. Tong, G. S. Brandt, M. Li, G. Shapovalov, E. Slimko, A. Karschin, D. A. Dougherty, and H. A. Lester (2001)
J. Gen. Physiol. 117, 103-118
   Abstract »    Full Text »    PDF »
Negative Factor from SIV Binds to the Catalytic Subunit of the V-ATPase to Internalize CD4 and to Increase Viral Infectivity.
R. Mandic, O. T. Fackler, M. Geyer, T. Linnemann, Y.-H. Zheng, and B. M. Peterlin (2001)
Mol. Biol. Cell 12, 463-473
   Abstract »    Full Text »
Vps10p Transport from the trans-Golgi Network to the Endosome Is Mediated by Clathrin-coated Vesicles.
O. Deloche, B. G. Yeung, G. S. Payne, and R. Schekman (2001)
Mol. Biol. Cell 12, 475-485
   Abstract »    Full Text »
PTH-Induced Downregulation of the Type IIa Na/Pi-Cotransporter Is Independent of Known Endocytic Motifs.
N. HERNANDO, J. FORGO, J. BIBER, and H. MURER (2000)
J. Am. Soc. Nephrol. 11, 1961-1968
   Abstract »    Full Text »
Distinct Trafficking Pathways Mediate Nef-Induced and Clathrin-Dependent Major Histocompatibility Complex Class I Down-Regulation.
S. Le Gall, F. Buseyne, A. Trocha, B. D. Walker, J.-M. Heard, and O. Schwartz (2000)
J. Virol. 74, 9256-9266
   Abstract »    Full Text »    PDF »
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.
L. X. Liu, N. Heveker, O. T. Fackler, S. Arold, S. Le Gall, K. Janvier, B. M. Peterlin, C. Dumas, O. Schwartz, S. Benichou, et al. (2000)
J. Virol. 74, 5310-5319
   Abstract »    Full Text »    PDF »
Identification of a Novel Member of the Chloride Intracellular Channel Gene Family (CLIC5) That Associates with the Actin Cytoskeleton of Placental Microvilli.
M. Berryman and A. Bretscher (2000)
Mol. Biol. Cell 11, 1509-1521
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Bi-directional trafficking between the trans-Golgi network and the endosomal/lysosomal system.
W. Rohn, Y Rouille, S Waguri, and B Hoflack (2000)
J. Cell Sci. 113, 2093-2101
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The Inhibitory Function of CTLA-4 Does Not Require Its Tyrosine Phosphorylation.
M. L. Baroja, D. Luxenberg, T. Chau, V. Ling, C. A. Strathdee, B. M. Carreno, and J. Madrenas (2000)
J. Immunol. 164, 49-55
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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.
C. S. Sevier, O. A. Weisz, M. Davis, and C. E. Machamer (2000)
Mol. Biol. Cell 11, 13-22
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Characterization of a Targeting Motif for a Flagellar Membrane Protein in Leishmania enriettii.
E. L. Snapp and S. M. Landfear (1999)
J. Biol. Chem. 274, 29543-29548
   Abstract »    Full Text »    PDF »
Crystal structure of the alpha appendage of AP-2 reveals a recruitment platform for clathrin-coat assembly.
L. M. Traub, M. A. Downs, J. L. Westrich, and D. H. Fremont (1999)
PNAS 96, 8907-8912
   Abstract »    Full Text »    PDF »



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