Why might a DNA binding protein cause a protein to be toxic to the cell?
TAR DNA-binding protein 43 (TDP-43) is an RNA-binding protein and a major component of protein aggregates found in amyotrophic lateral sclerosis and several other neurodegenerative diseases. TDP-43 exists as a full-length protein and as two shorter forms of 25 and 35 kDa. Full-length mutant TDP-43s found in amyotrophic lateral sclerosis patients re-localize from the nucleus to the cytoplasm and in part to mitochondria, where they exert a toxic role associated with neurodegeneration. However, induction of mitochondrial damage by TDP-43 fragments is yet to be clarified. In this work, we show that the mitochondrial 35 kDa truncated form of TDP-43 is restricted to the intermembrane space, while the full-length forms also localize in the mitochondrial matrix in cultured neuronal NSC-34 cells. Interestingly, the full-length forms clearly affect mitochondrial metabolism and morphology, possibly via their ability to inhibit the expression of Complex I subunits encoded by the mitochondrial-transcribed mRNAs, while the 35 kDa form does not. In the light of the known differential contribution of the full-length and short isoforms to generate toxic aggregates, we propose that the presence of full-length TDP-43s in the matrix is a primary cause of mitochondrial damage. This in turn may cause oxidative stress inducing toxic oligomers formation, in which short TDP-43 forms play a major role.
Why might a DNA binding protein cause a protein to be toxic to the cell?
1. A biochemist is attempting to separate a DNA-binding protein (protein X) from other proteins in a solution. Only three other proteins (A, B, and C) are present. The proteins have the following properties: pl (isoelectric point) Size Mr Bind to DNA? protein A 7.4 protein B 3.8 protein C 7.9 protein X7.8 82,000 21,500 23,000 22,000 yes yes no yes What type of protein separation techniques might she use to protein X from the other proteins. Give a flow...
Describe 2 reasons why the DNA major groove offers more specificity for protein binding.
DNA-binding proteins are proteins that are composed of DNA-binding domains and thus have a specific or general affinity for either single or double stranded DNA. Protein X is one such protein that binds to double stranded DNA. What residues are most likely to be located in the DNA binding site of protein X and why?
(2) In isolation, a DNA-binding protein binds to its regulatory sequence with a Kd of 1.0 M. Another DNA binding protein binds to another sequence on the same DNA a few bases away with a Kd of 5.0 HM when alone. The two proteins each have a domain which binds to the other with an interaction energy of -2.7 kcal/mole: (a) Draw the thermodynamic box which represents all four states of this system (b) what are the affinities for each...
Why might it be useful for a protein expression cell line such as the BL21 series, to have genes for several proteases knocked out?
HP1 is a DNA binding protein that interacts with a specific sequence (TGCTTATTC). You want to analyze, by a Dnase I footprinting assay, the effect on DNA binding of the interaction between HP1 and its 6 binding partner PA. In each assay, you combine a radiolabeled fragment of DNA that binds to HP1 and a specific combination of proteins. After incubation with DNase I, each reaction mixture was resolved by gel electrophoresis, and then exposed to film. The autoradiogram showing...
Explain why treatment of a preparation of E. coli single strand binding protein (SSB) with acetic anhydride produces a chemically modified protein that is unable to bind to DNA. [Hint: Acetic anhydride reacts with primary amino groups. Which amino acids would that include, and what would be the consequence of the reaction?] 3. Explain why treatment of a preparation of E. coli single strand binding protein (SSB) with acetic anhydride produces a chemically modified protein that is unable to bind...
The repressor protein for the Gal1 locus (does not / does) contain a DNA binding domain.
A change in DNA resulting in an incorrect protein is the problem in sickle cell disease. Is this normally the problem in genetic diseases? A. Yes, the DNA may be “correct” but can produce abnormal proteins which cause disease. B. No. In other genetic diseases, the proteins are all correctly made, but then they damage the DNA. C. No. Most genetic diseases result from errors in cell division. D. Yes, abnormal proteins created by abnormal DNA is the problem in...
The activity of would be quickly undone in the absence of single-stranded binding protein. O DNA polymerase | O DNA polymerase III O DNA ligase O DNA helicase O primase