3D Structure of **the SRY protein**

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C O N P S



A short tutorial on key features of the SRY protein

Here are a few key features:

Let's view the protein interacting with the DNA. The protein is in a ribbon display and the DNA is in a spacefill display.
In all probability, the DNA depicted in this chime image is the binding domain. A sequence with 100% binding affinity starting with nucleotide 60, is GTAGGGCACCCATTGTTCTCTCC.


Next, we are going to look at the sequence of nucleic acids that SRY protein binds to on the DNA.
Interestingly enough, when the DNA sequence is altered by one nucleotide and another is deleted, the binding affinity of SRY for DNA decreases from 100% to 10%.


Remember that normally, DNA is in a double helix that is more or less linear. Look closely at the following image.
Here, notice that the bottom of the DNA (depicted in white) is horizontal to the screen, and the top is vertical. SRY causes the DNA to bend like this. This is such a drastic conformational change that it causes the expression of certain genes that would not occur otherwise. This is exactly why SRY is sufficient for sexual determination. With this conformational change and the subsequent expression of certain genes, testes develop, which begins a cascade of different hormones that are associated with the XY phenotype.


With the nonsense mutation occuring at codon 107, trytophan has been changed to a stop signal. This is sufficient to keep SRY from binding to the DNA and the karyotype XY has a phenotype of XX. Tryptophan is purple, in the center of the alpha helix.


Here is the same view when bound to DNA.


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