Talk:P53-DNA Recognition

From Proteopedia

Ideas for improvement

This "figure-review" was written by Justin Lecuyer as part of an assignment for a Biochemistry course at Westfield State University, and posted by the instructor with permission.

1. My favorite figure: Figure “p53 tetramer binds DNA as a dimer of dimers”. The PDB ID is 3kz8, and the script is at http://www.proteopedia.org/wiki/scripts/P53DNA_Recognition/P53_complex/2.spt. The primary citation is found at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3280089/, .
2. This is my suggestion for a figure legend: P53-DNA Recognition (3kz8) binds as two homodimer subunits (magenta and cyan) to a DNA response element. Each magenta and cyan dimer forms a pair and binds to half of the DNA response element. The grey Zinc ions coordinate the surrounding nucleic acid residues and stabilize the fold of the DNA binding domain within the p53 protein.
3. What I like about the figure: I like that the figure color-codes the homodimer subunits of the tetramer. It also focuses on the DNA-binding domain of the protein, which is important because the whole purpose of the protein is to recognize specific sequences on the DNA.
4. Corresponding figure in the primary citation: Figure 2. In the figure, the protein is displayed in different orientations with regards to the core tetramers binding to the half sites on the DNA. The different views really allow for better understanding of the DNA-binding domain and show where bonds are likely to happen between arginine residues and the DNA.
5. How I think the figure could be improved: It would be better to have an image that shows arginine 248 interacting with the minor groove in the DNA as well as other residues within p53 interacting with the major groove in the DNA. Perhaps a button that will change those parts of the protein a different color. Arginine 248 is really important though because sources often talk about how mutations in this don’t allow the protein to bond correctly to the DNA which in turn supports tumor growth. Also, mutations in the Zn²⁺ ion lead to tumor growth because the zinc provides an interactions between three cystines and a histodine in the minor alpha helix that allow the protein to fold in an orientation that provide arginine 248 the opportunity to bind with the DNA. This is a key concept and I think the figure I mentioned previously is a good candidate to illustrate this.

References

Hollstein, Monica; Sidransky, David; Bogelstein, Bert; and Harris, Curtis. “p53 Mutations in Human Cancers”. Science. New Series, Vol. 253, No. 5015 (July 5, 1991. pp 49-53. Accessed 12/13/18.

Kitayner, Malka; Rozenberg, Haim; Rohs, Remo; Suad, Oded; Rabinovich, Dov; Honig, Barry; and Shakked, Zippora. “Diversity in DNA recognition by p53 revelaed by crystal structures with Hoogsteen base pairs”. Nat Struct Mol Biol. 2010 Apr; 17(4): 423-429. Accessed 12/10/18.

--Karsten Theis 19:18, 16 December 2018 (UTC)