Topology of a Human Equilibrative, Nitrobenzylthioinosine (NBMPR)-sensitive Nucleoside Transporter (hENT1) Implicated in the Cellular Uptake of Adenosine and Anti-cancer Drugs
| Autor: | Stephen A. Baldwin, Manickavasagam Sundaram, Jean C. Ingram, Carol E. Cass, Zoe A. Berry, Fatima Abidi, James D. Young, Sylvia Y.M. Yao |
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| Rok vydání: | 2001 |
| Předmět: |
Cytoplasm
Adenosine Glycosylation Xenopus Immunoblotting Antineoplastic Agents Enzyme-Linked Immunosorbent Assay Equilibrative nucleoside transporter 2 Nucleoside transporter Biochemistry Equilibrative Nucleoside Transporter 1 Thioinosine Animals Humans Amino Acids Molecular Biology Integral membrane protein Dose-Response Relationship Drug biology Cell Membrane Membrane Transport Proteins Biological Transport Equilibrative nucleoside transporter Cell Biology Immunohistochemistry Recombinant Proteins Transmembrane protein Protein Structure Tertiary Transmembrane domain Membrane topology biology.protein Nucleoside Algorithms Software |
| Zdroj: | Journal of Biological Chemistry. 276:45270-45275 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m107169200 |
| Popis: | The human equilibrative nucleoside transporter hENT1, the first identified member of the ENT family of integral membrane proteins, is the primary mechanism for the cellular uptake of physiologic nucleosides, including adenosine, and many anti-cancer nucleoside drugs. We have produced recombinant hENT1 in Xenopus oocytes and used native and engineered N-glycosylation sites in combination with immunological approaches to experimentally define the membrane architecture of this prototypic nucleoside transporter. hENT1 (456 amino acid residues) is shown to contain 11 transmembrane helical segments with an amino terminus that is intracellular and a carboxyl terminus that is extracellular. Transmembrane helices are linked by short hydrophilic regions, except for a large glycosylated extracellular loop between transmembrane helices 1 and 2 and a large central cytoplasmic loop between transmembrane helices 6 and 7. Sequence analyses suggest that this membrane topology is common to all mammalian, insect, nematode, protozoan, yeast, and plant members of the ENT protein family. |
| Databáze: | OpenAIRE |
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