20.109:W/F Green Team: Difference between revisions
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|A "Silent" Polymorphism in the MDR1 Gene Changes Substrate Specificity | |A "Silent" Polymorphism in the MDR1 Gene Changes Substrate Specificity | ||
Chava Kimchi-Sarfaty, Jung Mi Oh, In-Wha Kim, Zuben E. Sauna, Anna Maria Calcagno, Suresh V. Ambudkar, and Michael M. Gottesman (26 January 2007) | Chava Kimchi-Sarfaty, Jung Mi Oh, In-Wha Kim, Zuben E. Sauna, Anna Maria Calcagno, Suresh V. Ambudkar, and Michael M. Gottesman (26 January 2007) || | ||
[http://www.sciencemag.org/cgi/content/abstract/1135308 Paper]|| | |||
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. | |||
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Revision as of 15:00, 3 May 2007
Oral Presentation Outline
Summary
Single nucleotide polymorphisms which are traditionally considered silent (coding for same amino acid) can effect protein folding. We have always been taught to believe that these silent mutations are just that, silent. The fact that they can change protein structure and subsequent function could lead to a much more thorough analysis of DNA mutations and could give us new insight as to how things are mutated.
We want to design a peptide which has several points for silent mutations which are known to create structural differences in proteins. We then want to test the effects of mutating this peptide is humans, yeast and M13.
Info | Link | Notes |
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Pearson H. Silent Mutations Speak Up. Nature. | Paper |
Overview of Silent SNPs |
Richards AJ et al. Missense and silent mutations in COL2A1 result in Stickler syndrome but via different molecular mechanisms. Human Mutation.2007 Apr 16;28(6):639 | Paper | |
A "Silent" Polymorphism in the MDR1 Gene Changes Substrate Specificity
Chava Kimchi-Sarfaty, Jung Mi Oh, In-Wha Kim, Zuben E. Sauna, Anna Maria Calcagno, Suresh V. Ambudkar, and Michael M. Gottesman (26 January 2007) || Paper|| 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. |