Science (American Association for the Advancement of Science), 2007-01, Vol.315 (5811), p.525-528
2007
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Details
- Autor(en) / Beteiligte
- Titel
- A "Silent" Polymorphism in the MDR1 Gene Changes Substrate Specificity
- Ist Teil von
- Science (American Association for the Advancement of Science), 2007-01, Vol.315 (5811), p.525-528
- Ort / Verlag
- Washington, DC: American Association for the Advancement of Science
- Erscheinungsjahr
- 2007
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Synonymous single-nucleotide polymorphisms (SNPs) do not produce altered coding sequences, and therefore they are not expected to change the function of the protein in which they occur. We report that a synonymous SNP in the Multidrug Resistance 1 (MDR1) gene, part of a haplotype previously linked to altered function of the MDR1 gene product P-glycoprotein (P-gp), nonetheless results in P-gp with altered drug and inhibitor interactions. Similar mRNA and protein levels, but altered conformations, were found for wild-type and polymorphic P-gp. We hypothesize that the presence of a rare codon, marked by the synonymous polymorphism, affects the timing of cotranslational folding and insertion of P-gp into the membrane, thereby altering the structure of substrate and inhibitor interaction sites.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0036-8075eISSN: 1095-9203DOI: 10.1126/science.1135308Titel-ID: cdi_proquest_miscellaneous_36218815
- Format
- –
- Schlagworte
- Animals, ATP-Binding Cassette, Sub-Family B, Member 1 - antagonists & inhibitors, ATP-Binding Cassette, Sub-Family B, Member 1 - chemistry, ATP-Binding Cassette, Sub-Family B, Member 1 - genetics, ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism, Biological and medical sciences, Cell Line, Cell lines, Cell Membrane - metabolism, Cell physiology, Cells, Cercopithecus aethiops, Codon, Codons, Cyclosporine - pharmacology, Epithelial cells, Fluorescence, Fundamental and applied biological sciences. Psychology, Genes, MDR, Genetics, Haplotypes, HeLa Cells, Humans, Hypotheses, Immatures, Kidney cells, Membrane and intracellular transports, Messenger RNA, Molecular and cellular biology, Mutagenesis, Site-Directed, Polymorphism, Polymorphism, Single Nucleotide, Protein Biosynthesis, Protein Conformation, Protein Folding, Protein Structure, Tertiary, Proteins, Reverse Transcriptase Polymerase Chain Reaction, Rhodamine 123 - metabolism, Rhodamine 123 - pharmacology, RNA, Messenger - genetics, RNA, Messenger - metabolism, Sirolimus - pharmacology, Substrate Specificity, Transfection, Verapamil - metabolism, Verapamil - pharmacology